Benedicte Alexandra Lie

• Gansmo, Liv Beathe; Lie, Benedicte Alexandra; Mæhlen, Marthe Thoresen; Vatten, Lars Johan; Romundstad, Pål Richard; Hveem, Kristian; Lønning, Per Eystein & Knappskog, Stian (2021). Polymorphisms in the TP53-MDM2-MDM4-axis in patients with rheumatoid arthritis. Gene.  ISSN 0378-1119.  793:145747, s 1- 9 . doi: 10.1016/j.gene.2021.145747
• Heinicke, Fatima; Zhong, Xiangfu; Flåm, Siri Tennebø; Breidenbach, Johannes; Leithaug, Magnus; Mæhlen, Marthe Thoresen; Lillegraven, Siri; Aga, Anna-Birgitte; Norli, Ellen Sauar; Mjaavatten, Maria Dahl; Haavardsholm, Espen Andre; Zucknick, Manuela; Rayner, Simon & Lie, Benedicte Alexandra (2021). MicroRNA Expression Differences in Blood-Derived CD19+ B Cells of Methotrexate Treated Rheumatoid Arthritis Patients. Frontiers in Immunology.  ISSN 1664-3224.  12 . doi: 10.3389/fimmu.2021.663736 Fulltekst i vitenarkiv. Vis sammendrag

  Rheumatoid arthritis (RA) is a complex disease with a wide range of underlying susceptibility factors. Recently, dysregulation of microRNAs (miRNAs) in RA have been reported in several immune cell types from blood. However, B cells have not been studied in detail yet. Given the autoimmune nature of RA with the presence of autoantibodies, CD19+ B cells are a key cell type in RA pathogenesis and alterations in CD19+ B cell subpopulations have been observed in patient blood. Therefore, we aimed to reveal the global miRNA repertoire and to analyze miRNA expression profile differences in homogenous RA patient phenotypes in blood-derived CD19+ B cells. Small RNA sequencing was performed on CD19+ B cells of newly diagnosed untreated RA patients (n=10), successfully methotrexate (MTX) treated RA patients in remission (MTX treated RA patients, n=18) and healthy controls (n=9). The majority of miRNAs was detected across all phenotypes. However, significant expression differences between MTX treated RA patients and controls were observed for 27 miRNAs, while no significant differences were seen between the newly diagnosed patients and controls. Several of the differentially expressed miRNAs were previously found to be dysregulated in RA including miR-223-3p, miR-486-3p and miR-23a-3p. MiRNA target enrichment analysis, using the differentially expressed miRNAs and miRNA-target interactions from miRTarBase as input, revealed enriched target genes known to play important roles in B cell activation, differentiation and B cell receptor signaling, such as STAT3, PRDM1 and PTEN. Interestingly, many of those genes showed a high degree of correlated expression in CD19+ B cells in contrast to other immune cell types. Our results suggest important regulatory functions of miRNAs in blood-derived CD19+ B cells of MTX treated RA patients and motivate for future studies investigating the interactive mechanisms between miRNA and gene targets, as well as the possible predictive power of miRNAs for RA treatment response.

• Sandling, Johanna K.; Pucholt, Pascal; Hultin Rosenberg, Lina; Farias, Fabiana H.G.; Kozyrev, Sergey V.; Eloranta, Maija-Leena; Alexsson, Andrei; Bianchi, Matteo; Padyukov, Leonid; Bengtsson, Christine; Jonsson, Roland; Omdal, Roald; Lie, Benedicte Alexandra; Massarenti, Laura; Steffensen, Rudi; Jakobsen, Marianne A.; Lillevang, Søren T.; Lerang, Karoline; Molberg, Øyvind; Voss, Anne; Troldborg, Anne; Jacobsen, Søren; Syvänen, Ann-Christine; Jönsen, Andreas; Gunnarsson, Iva; Svenungsson, Elisabet; Rantapää-Dahlqvist, Solbritt; Bengtsson, Anders A.; Sjöwall, Christopher; Leonard, Dag; Lindblad-Toh, Kerstin & Rönnblom, Lars (2021). Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  80, s 109- 117 . doi: 10.1136/annrheumdis-2020-218636
• Gjefsen, Elisabeth; Bråten, Lars Christian Haugli; Goll, Guro Løvik; Wigemyr, Monica; Bolstad, Nils; Valberg, Morten; Schistad, Ellina Iordanova; Marchand, Gunn Hege; Granviken, Fredrik; Selmer, Kaja Kristine; Johanessen, Anne Froholdt; Haugen, Anne Julsrud; Dagestad, Magnhild Hammersland; Vetti, Nils; Bakland, Gunnstein; Lie, Benedicte Alexandra; Haavardsholm, Espen A.; Nilsen, Aksel Thuv; Holmgard, Thor Einar; Kadar, Thomas; Kvien, Tore Kristian; Skouen, Jan Sture; Grøvle, Lars; Brox, Jens Ivar; Espeland, Ansgar; Storheim, Kjersti & Zwart, John-Anker (2020). The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial. BMC Musculoskeletal Disorders.  ISSN 1471-2474.  21:698, s 1- 14 . doi: 10.1186/s12891-020-03720-5 Fulltekst i vitenarkiv.
• Guderud, Kari; Sunde, Line Hagen; Flåm, Siri Tennebø; Mæhlen, Marthe Thoresen; Mjaavatten, Maria Dahl; Lillegraven, Siri; Aga, Anna-Birgitte; Evenrød, Ida Marie; Norli, Ellen Sauar; Andreassen, Bettina Kulle; Franzenburg, Sören; Franke, Andre; Haavardsholm, Espen Andre; Rayner, Simon; Gervin, Kristina & Lie, Benedicte Alexandra (2020). Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DNA Methylation Differences in CD4+ Memory Than in CD4+ Naïve T Cells. Frontiers in Immunology.  ISSN 1664-3224.  11:194, s 1- 14 . doi: 10.3389/fimmu.2020.00194 Fulltekst i vitenarkiv.
• Heinicke, Fatima; Zhong, Xiangfu; Zucknick, Karola Manuela; Breidenbach, Johannes; Sundaram, Arvind Yegambaram Meenakshi; Flåm, Siri Tennebø; Leithaug, Magnus; Dalland, Marianne; Rayner, Simon; Lie, Benedicte Alexandra & Gilfillan, Gregor (2020). An extension to: Systematic assessment of commercially available low-input miRNA library preparation kits. RNA Biology.  ISSN 1547-6286.  17(9), s 1284- 1292 . doi: 10.1080/15476286.2020.1761081 Fulltekst i vitenarkiv. Vis sammendrag

  High-throughput sequencing has emerged as the favoured method to study microRNA (miRNA) expression, but biases introduced during library preparation have been reported. We recently compared the performance (sensitivity, reliability, titration response and differential expression) of six commercially-available kits on synthetic miRNAs and human RNA, where library preparation was performed by the vendors. We hereby supplement this study with data from two further commonly used kits (NEBNext, NEXTflex) whose manufacturers initially declined to participate. NEXTflex demonstrated the highest sensitivity, which may reflect its use of partially-randomized adapter sequences, but overall performance was lower than the QIAseq and TailorMix kits. NEBNext showed intermediate performance. We reaffirm that biases are kit specific, complicating the comparison of miRNA datasets generated using different kits.

• Helgeland, Hanna; Gabrielsen, Ingvild Synnøve Matre; Akselsen, Helle; Meenakshi Sundaram, Arvind Yegambaram; Flåm, Siri Tennebø & Lie, Benedicte Alexandra (2020). Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells. BMC Genomics.  ISSN 1471-2164.  21(350) . doi: 10.1186/s12864-020-6755-1 Fulltekst i vitenarkiv. Vis sammendrag

  Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery. Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. The thymic T cells showed the largest number of uniquely expressed genes, suggesting a more diverse transcription in thymic T cells. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression. Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to primary blood derived T cells. Interestingly, the majority of autoimmune disease associated genes were expressed in one or more T cell subset, however ~ 11% of these were not expressed in frequently studied adult peripheral blood.

• Juvodden, Hilde Therese; Viken, Marte Kathrine; Nordstrand, Sebjørg Elizabeth Hesla; Viste, Rannveig; Westlye, Lars Tjelta; Thorsby, Per Medbøe; Lie, Benedicte Alexandra & Knudsen, Stine (2020). HLA and sleep parameter associations in post-H1N1 narcolepsy type 1 patients and first-degree relatives. Sleep.  ISSN 0161-8105.  43(3), s 1- 11 . doi: 10.1093/sleep/zsz239 Fulltekst i vitenarkiv.
• Lande, Asgeir; Fluge, Øystein; Strand, Elin Bolle; Flåm, Siri Tennebø; Daysi Duarte, Sosa; Mella, Olav; Egeland, Torstein; Saugstad, Ola Didrik; Lie, Benedicte Alexandra & Viken, Marte K (2020). Human Leukocyte Antigen Alleles Associated With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Scientific Reports.  ISSN 2045-2322.  10:5267(1), s 1- 8 . doi: 10.1038/s41598-020-62157-x Fulltekst i vitenarkiv.
• Rekeland, Ingrid Gurvin; Fosså, Alexander; Lande, Asgeir; Ktoridou-Valen, Irini; Sørland, Kari; Holsen, Mari Helgesen; Tronstad, Karl Johan; Risa, Kristin; Alme, Kine; Viken, Marte Katrine; Lie, Benedicte Alexandra; Dahl, Olav; Mella, Olav & Fluge, Øystein (2020). Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Frontiers in medicine.  ISSN 2296-858X.  7:162, s 1- 15 . doi: 10.3389/fmed.2020.00162 Fulltekst i vitenarkiv.
• Tapia, German; Mortimer, Georgina; Ye, Jody; Mårild, Karl Staffan; Chipper-Keating, Saranna; Gillard, Benjamin Thomas; Viken, Marte Katrine; Lie, Benedicte Alexandra; Stene, Lars Christian Mørch; Gillespie, Kathleen & Størdal, Ketil (2020). Maternal microchimerism in cord blood and risk of celiac disease in childhood. Journal of Pediatric Gastroenterology and Nutrition - JPGN.  ISSN 0277-2116.  71(3), s 321- 327 . doi: 10.1097/MPG.0000000000002811 Fulltekst i vitenarkiv.
• Bråten, Lars Christian Haugli; Rolfsen, Mads Peder; Espeland, Ansgar; Wigemyr, Monica; Assmus, Jörg; Froholdt, Anne; Haugen, Anne Julsrud; Marchand, Gunn Hege; Kristoffersen, Per M; Lutro, Olav; Randen, Sigrun; Wilhelmsen, Maja; Winsvold, Bendik K S; Kadar, Thomas; Holmgard, Thor Einar; Vigeland, Maria Dehli; Vetti, Nils; Nygaard, Øystein Petter; Lie, Benedicte Alexandra; Hellum, Christian; Anke, Audny; Grotle, Margreth; Schistad, Ellina Iordanova; Skouen, Jan Sture; Grøvle, Lars; Brox, Jens Ivar; Zwart, John-Anker & Storheim, Kjersti (2019). Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. BMJ. British Medical Journal.  ISSN 1756-1833.  367 . doi: 10.1136/bmj.l5654 Fulltekst i vitenarkiv. Vis sammendrag

  Objective To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). Design Double blind, parallel group, placebo controlled, multicentre trial. Setting Hospital outpatient clinics at six hospitals in Norway. Participants 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. Interventions Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. Main outcome measures The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. Results In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was −1.6 (95% confidence interval −3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was −2.3 (−4.2 to−0.4, P=0.02) for patients with type 1 Modic changes and −0.1 (−2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. Conclusions In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes.

• Gabrielsen, Ingvild Synnøve Matre; Helgeland, Hanna; Akselsen, Helle; Aass, Hans Christian Dalsbotten; Meenakshi Sundaram, Arvind Yegambaram; Snowhite, Isaac V.; Pugliese, Alberto; Flåm, Siri Tennebø & Lie, Benedicte Alexandra (2019). Transcriptomes of antigen presenting cells in human thymus. PLOS ONE.  ISSN 1932-6203.  14:e0218858(7), s 1- 18 . doi: 10.1371/journal.pone.0218858 Fulltekst i vitenarkiv.
• Heinicke, Fatima; Zhong, Xiangfu; Zucknick, Manuela; Breidenbach, Johannes; Sundaram, Arvind Yegambaram Meenakshi; Flåm, Siri Tennebø; Leithaug, Magnus; Dalland, Marianne; Farmer, Andrew; Henderson, Jordana M.; Hussong, Melanie A.; Moll, Pamela; Nguyen, Loan; McNulty, Amanda; Shaffer, Jonathan M.; Shore, Sabrina; Yip, Hoichong Karen; Vitkovska, Jana; Rayner, Simon; Lie, Benedicte Alexandra & Gilfillan, Gregor Duncan (2019). Systematic assessment of commercially available low-input miRNA library preparation kits. RNA Biology.  ISSN 1547-6286.  17(1), s 75- 86 . doi: 10.1080/15476286.2019.1667741 Fulltekst i vitenarkiv. Vis sammendrag

  High-throughput sequencing is increasingly favoured to assay the presence and abundance of microRNAs (miRNAs) in biological samples, even from low RNA amounts, and a number of commercial vendors now offer kits that allow miRNA sequencing from sub-nanogram (ng) inputs. Although biases introduced during library preparation have been documented, the relative performance of current reagent kits has not been investigated in detail. Here, six commercial kits capable of handling <100ng total RNA input were used for library preparation, performed by kit manufactures, on synthetic miRNAs of known quantities and human total RNA samples. We compared the performance of miRNA detection sensitivity, reliability, titration response and the ability to detect differentially expressed miRNAs. In addition, we assessed the use of unique molecular identifiers (UMI) sequence tags in one kit. We observed differences in detection sensitivity and ability to identify differentially expressed miRNAs between the kits, but none were able to detect the full repertoire of synthetic miRNAs. The reliability within the replicates of all kits was good, while larger differences were observed between the kits, although none could accurately quantify the relative levels of the majority of miRNAs. UMI tags, at least within the input ranges tested, offered little advantage to improve data utility. In conclusion, biases in miRNA abundance are heavily influenced by the kit used for library preparation, suggesting that comparisons of datasets prepared by different procedures should be made with caution. This article is intended to assist researchers select the most appropriate kit for their experimental conditions.

• Kjeldsen-Kragh, Jens; Titze, Thomas Larsen; Lie, Benedicte Alexandra; Vaage, John T. & Kjær, Mette (2019). HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a-immunized women. Blood Advances.  ISSN 2473-9529.  3(7), s 945- 951 . doi: 10.1182/bloodadvances.2019032227 Fulltekst i vitenarkiv. Vis sammendrag

  HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [Pglobal] = .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother’s HLA-DRB3*01:01 allele on the platelet count of the newborn (Pglobal = .0155). Median (range) neonatal platelet counts were 241 × 109/L (59 × 109/L to 393 × 109/L), 107 × 109/L (4 × 109/L to 387 × 109/L) and 32 × 109/L (4 × 109/L to 352 × 109/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a–immunized women.

• López-Isac, Elena; Acosta-Herrera, Marialbert; Kerick, Martin; Assassi, Shervin; Satpathy, Ansuman T.; Granja, Jeffrey; Mumbach, Maxwell R.; Beretta, Lorenzo; Simeón, Carmen P.; Carreira, Patricia; Ortego-Centeno, Norberto; Castellvi, Ivan; Bossini-Castillo, Lara; Carmona, Francisco David; Orozco, Gisela; Hunzelmann, Nicolas; Distler, Jörg H.W.; Franke, Andre; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; de Vries-Bouwstra, Jeska; Wijmenga, Cisca; Koeleman, Bobby P.C.; Nordin, Annika; Padyukov, Leonid; Hoffmann-Vold, Anna-Maria; Lie, Benedicte Alexandra; Proudman, Susanna; Stevens, Wendy; Nikpour, Mandana; Vyse, Timothy; Herrick, Ariane L.; Worthington, Jane; Denton, Christopher P.; Allanore, Yannick; Brown, Matthew A.; Radstake, Timothy R.D.J.; Fonseca, Carmen; Chang, Howard Y.; Mayes, Maureen D. & Martin, Javier (2019). GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways. Nature Communications.  ISSN 2041-1723.  10:4955, s 1- 14 . doi: 10.1038/s41467-019-12760-y Fulltekst i vitenarkiv.
• Tapia, German; Mortimer, Georgina; Ye, Jody; Gillard, Benjamin Thomas; Chipper-Keating, Saranna; Mårild, Karl Staffan; Viken, Marte K; Lie, Benedicte Alexandra; Joner, Geir; Skrivarhaug, Torild; Njølstad, Pål Rasmus; Størdal, Ketil; Gillespie, Kathleen & Stene, Lars Christian Mørch (2019). Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes. Pediatric Diabetes.  ISSN 1399-543X.  20(6), s 728- 735 . doi: 10.1111/pedi.12875 Fulltekst i vitenarkiv.
• Tapia, German; Mårild, Karl Staffan; Dahl, Sandra Rinne; Lund-Blix, Nicolai Andre; Viken, Marte K; Lie, Benedicte Alexandra; Njølstad, Pål Rasmus; Joner, Geir; Skrivarhaug, Torild; Cohen, Arieh S.; Størdal, Ketil & Stene, Lars Christian Mørch (2019). Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes. Diabetes Care.  ISSN 0149-5992.  42(4), s 553- 559 . doi: 10.2337/dc18-2176 Fulltekst i vitenarkiv.
• Zhong, Xiangfu; Heinicke, Fatima; Lie, Benedicte Alexandra & Rayner, Simon (2019). Accurate Adapter Information Is Crucial for Reproducibility and Reusability in Small RNA Seq Studies. Non-coding RNA.  ISSN 2311-553X. . doi: 10.3390/ncrna5040049 Fulltekst i vitenarkiv.
• Guderud, Kari; Mæhlen, Marthe Thoresen; Namløs, Gry Beate; Viken, Marte K; Kulle, Bettina; Molberg, Øyvind; Flåm, Siri Tennebø & Lie, Benedicte Alexandra (2018). Lack of association among peptidyl arginine deiminase type 4 autoantibodies, PADI4 polymorphisms, and clinical characteristics in rheumatoid arthritis. Journal of Rheumatology.  ISSN 0315-162X.  45(9), s 1211- 1219 . doi: 10.3899/jrheum.170769 Vis sammendrag

  Objective.We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the PADI4 gene together with clinical variables in rheumatoid arthritis (RA). Methods. Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 available from previous studies). Genotyping of PADI4 was performed using TaqMan assays in 945 patients and 1118 controls. Clinical data, anticitrullinated protein antibodies (ACPA) status, shared epitope status, and a combined genetic risk score were also available. Results. Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also ACPA-positive. No association was observed between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status. Conclusion. Taken together, the results from these combined serological, genetic, and clinical analyses suggest that anti-PAD4 appears to be a bystander autoantibody with no current clinical utility in RA. (First Release June 1 2018; J Rheumatol 2018;45:1211–19; doi:10.3899/jrheum.170769)

• Lande, Asgeir; Andersen, Irene; Egeland, Torstein; Lie, Benedicte Alexandra & Viken, Marte K (2018). HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians. Human Immunology.  ISSN 0198-8859.  79(7), s 527- 529 . doi: 10.1016/j.humimm.2018.04.012
• Mitrovic, Mitja; Patsopoulos, Nikolaos A.; Beecham, Ashley H.; Dankowski, Theresa; Goris, An; Dubois, Benedicte; D’hooghe, Marie B.; Lemmens, Robin; Van Damme, Philip; Bach Søndergaard, Helle; Sellebjerg, Finn; Soelberg Sorensen, Per; Ullum, Henrik; Thørner, Lise Wegner; Werge, Thomas; Saarela, Janna; Cournu-Rebeix, Isabelle; Damotte, Vincent; Fontaine, Bertrand; Guillot-Noel, Lena; Lathrop, Mark; Vukusik, Sandra; Gourraud, Pierre-Antoine; Andlauer, Till F.M.; Pongratz, Viola; Buck, Dorothea; Gasperi, Christiane; Antonios, Bayas; Heesen, Christoph; Kümpfel, Tania; Linker, Ralf; Paul, Friedemann; Stangel, Martin; Tackenberg, Björn; Bergh, Florian Then; Warnke, Clemens; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe; Ziemann, Ulf; Tumani, Hayrettin; Gold, Ralf; Grummel, Verena; Hemmer, Bernhard; Knier, Benjamin; Lill, Christina M.; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen; Lie, Benedicte Alexandra; Spurkland, Anne; Harbo, Hanne Flinstad & Cotsapas, Chris (2018). Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell.  ISSN 0092-8674.  175(6), s 1679- 1687 . doi: 10.1016/j.cell.2018.09.049 Fulltekst i vitenarkiv.
• Størdal, Ketil; McArdle, Harry J.; Hayes, Helen; Tapia, German; Viken, Marte K; Lund-Blix, Nicolai Andre; Haugen, Margaretha; Joner, Geir; Skrivarhaug, Torild; Mårild, Karl Staffan; Njølstad, Pål Rasmus; Eggesbø, Merete Åse; Mandal, Siddhartha; Page, Christian; London, Stephanie J.; Lie, Benedicte Alexandra & Stene, Lars Christian Mørch (2018). Prenatal iron exposure and childhood type 1 diabetes. Scientific Reports.  ISSN 2045-2322.  8 . doi: 10.1038/s41598-018-27391-4 Fulltekst i vitenarkiv.
• Henriksen, Eva Kristine Klemsdal; Viken, Marte K; Wittig, Michael; Holm, Kristian; Folseraas, Trine; Mucha, Sören; Melum, Espen; Hov, Johannes Espolin Roksund; Lazaridis, Konstantinos N.; Juran, Brian D.; Chazouillères, Olivier; Färkkilä, Martti A.; Gotthardt, Daniel Nils; Invernizzi, Pietro; Carbone, Marco; Hirschfield, Gideon Morris; Rushbrook, Simon Matthew; Goode, Elizabeth C.; Ponsioen, Cyriel Y.; Weersma, Rinse K.; Eksteen, Bertus; Yimam, Kidist K.; Gordon, Stuart C.; Goldberg, David E.; Yu, Lei; Bowlus, Christopher L.; Franke, Andre; Lie, Benedicte Alexandra & Karlsen, Tom Hemming (2017). HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry. HLA.  ISSN 2059-2302.  90(4), s 228- 233 . doi: 10.1111/tan.13076
• Hov, Johannes Espolin Roksund; Boberg, Kirsten Muri; Taraldsrud, Eli; Vesterhus, Mette; Boyadzhieva, Maria; Solberg, Inger Camilla; Schrumpf, Erik; Vatn, Morten H; Lie, Benedicte Alexandra; Molberg, Øyvind & Karlsen, Tom Hemming (2017). Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis. Liver international (Print).  ISSN 1478-3223.  37(3), s 458- 465 . doi: 10.1111/liv.13238
• Mårild, Karl; Tapia, German; Haugen, Margaretha; Dahl, Sandra Rinne; Cohen, Arieh S.; Lundqvist, Marika; Lie, Benedicte Alexandra; Stene, Lars Christian & Størdal, Ketil (2017). Maternal and neonatal vitamin D status, genotype and childhood celiac disease. PLOS ONE.  ISSN 1932-6203.  12(7) . doi: 10.1371/journal.pone.0179080 Fulltekst i vitenarkiv.
• Popperud, Trine Haug; Viken, Marte K; Kerty, Emilia & Lie, Benedicte Alexandra (2017). Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset. PLOS ONE.  ISSN 1932-6203.  12:e0186383(10), s 1- 9 . doi: 10.1371/journal.pone.0186383
• Størdal, Ketil; Mårild, Karl; Tapia, German; Haugen, Margaretha; Cohen, Arieh S; Lie, Benedicte Alexandra & Stene, Lars Christian (2017). Fetal and maternal genetic variants influencing neonatal vitamin D status. Journal of Clinical Endocrinology and Metabolism.  ISSN 0021-972X.  102(11), s 4072- 4079 . doi: 10.1210/jc.2017-00827
• Viken, Marte K; Flåm, Siri Tennebø; Skrivarhaug, Torild; Amundsen, Silja Svanstrøm; Sollid, Ludvig Magne; Drivvoll, Ann Kristin; Joner, Geir; Dahl-Jørgensen, Knut & Lie, Benedicte Alexandra (2017). HLA class II alleles in Norwegian patients with coexisting type 1 diabetes and celiac disease. HLA.  ISSN 2059-2302.  89(5), s 278- 284 . doi: 10.1111/tan.12986
• Witoelar, Aree; Jansen, Iris E.; Wang, Yunpeng; Desikan, Rahul S.; Gibbs, J. Raphael; Thompson, Wesley Kurt; Hernandez, Dena G.; Djurovic, Srdjan; Schork, Andrew J.; Bettella, Francesco; Ellinghaus, David; Franke, Andre; Lie, Benedicte Alexandra; McEvoy, Linda K.; Karlsen, Tom Hemming; Lesage, Suzanne; Morris, Huw R.; Brice, Alexis; Wood, Nicholas W.; Heutink, Peter; Hardy, John; Singleton, Andrew B.; Dale, Anders; Gasser, Thomas; Andreassen, Ole Andreas & Sharma, Manu (2017). Genome-wide pleiotropy between Parkinson disease and autoimmune diseases. JAMA Neurology.  ISSN 2168-6149.  74(7), s 780- 792 . doi: 10.1001/jamaneurol.2017.0469
• Carmona, David; Vaglio, Augusto; Mackie, Sarah L; Hernández-Rodríguez, José; Monarch, Paul A; Castaneda, Santos; Solans, Roser; Morado, Inmaculada C.; Narváez, Javier; Ramentol-Sintas, Marc; Pease, Colin T.; Dasgupta, Bhaskar; Watts, Richard; Khalidi, Nader A.; Langford, Carol A.; Ytterberg, Steven R.; Boiardi, Luigi; Beretta, Lorenzo; Govone, Marcello; Emmi, Giacomo; Bonatti, Francesco; Cimmino, Marco A.; Witte, Torsten; Neuman, Thomas; Holle, Julia; Schönau, Verena; Sailler, Laurent; Papo, Thomas; Haroche, Julien; Mahr, Alfred; Mouthon, Luc; Molberg, Øyvind; Diamantopoulos, Andreas P; Voskuyl, Alexandre; Brouwer, Elisabeth; Daikeler, Thomas; Berger, Christoph T; Molloy, Eamonn S; O'Neill, Lorraine; Blockmans, Daniel; Lie, Benedicte Alexandra; McLaren, Paul; Vyse, Timothy J.; Wijmenga, Cisca; Allanore, Yannick & Martin, Javier (2016). A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis. American Journal of Human Genetics.  ISSN 0002-9297.  100(1), s 64- 74 . doi: 10.1016/j.ajhg.2016.11.013
• Dominguez Valentin, Mev; Gras Navarro, Andrea; Rahman, Mohummad Aminur; Kumar, Surendra; Retière, Christèle; Ulvestad, Elling; Kristensen, Vessela N.; Lund-Johansen, Morten; Lie, Benedicte Alexandra; Enger, Per Øyvind; Njølstad, Gro; Kristoffersen, Einar Klæboe; Lie, Stein Atle & Chekenya, Martha (2016). Identification of a natural killer cell receptor allele that prolongs survival of cytomegalovirus-positive glioblastoma patients. Cancer Research.  ISSN 0008-5472.  76(18), s 5326- 5336 . doi: 10.1158/0008-5472.CAN-16-1162
• Finkel, Terri H.; Li, Jin; Wei, Zhi; Wang, Wei; Zhang, Haitao; Behrens, Edward M.; Reuschel, Emma L.; Limou, Sophie; Wise, Carol; Punaro, Marilynn; Becker, Mara L.; Munro, Jane E.; Flatø, Berit; Førre, Øystein Thorleiv; Thompson, Susan D.; Langefeld, Carl D.; Glass, David N.; Glessner, Joseph T.; Kim, Cecilia E.; Frackelton, Edward; Shivers, Debra K.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Hou, Cuiping; Xu, Kexiang; Snyder, James; Qiu, Haijun; Mentch, Frank; Wang, Kai; Winkler, Cheryl A.; Lie, Benedicte Alexandra; Ellis, Justine A. & Hakonarson, Hakon (2016). Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Medical Genetics.  ISSN 1471-2350.  17(1) . doi: 10.1186/s12881-016-0285-3
• Gabrielsen, Ingvild; Amundsen, Svanstrøm Silja; Helgeland, Hanna; Flåm, Siri Tennebø; Hatinoor, Nimo; Holm, Kristian; Viken, Marte K & Lie, Benedicte Alexandra (2016). Genetic risk variants for autoimmune diseases that influence gene expression in thymus. Human Molecular Genetics.  ISSN 0964-6906.  25(14), s 3117- 3124 . doi: 10.1093/hmg/ddw152 Vis sammendrag

  Genome-wide association studies (GWAS) have boosted our knowledge of genetic risk variants in autoimmune diseases (AIDs). Most risk variants are located within or near genes with immunological functions, and the majority is found to be non-coding, pointing towards a regulatory role. In this study, we performed a cis expression quantitative trait locus (eQTL) screen restricted to 353 AID associated risk variants selected from the GWAS catalog to investigate whether these single nucleotide polymorphisms (SNPs) influence gene expression in thymus. Genotypes were obtained by Immunochip (Ichip) and tested against expression of surrounding genes (±1 Mb) in human thymic tissue (n = 42). We identified eight significant eQTLs located within seven genetic regions (FCRL3, RNASET2, C2orf74, NPIPB8, SIRPG, SYS1 and AJ006998.2) where the expression was associated with AID risk SNPs at a study-wide level of significance (P < 2.7 × 10-5). In NPIPB8 and AJ006998.2, the eQTL signals appeared to be thymus-specific. Furthermore, many AID risk SNPs from GWAS have been subsequently fine-mapped in recent Ichip projects, and fine-mapped AID SNPs overlapped with the thymic eQTLs within RNASET2 and SIRPG Finally, in all the eQTL regions, except C2orf74, SNPs underlying the thymic eQTLs were predicted to interfere with transcription factors important in T cell development. Our study therefore reveals autoimmune risk variants that act as eQTLs in thymus, and suggest that thymic gene regulation may play a functional role at some AID risk loci.

• Gabrielsen, Ingvild; Viken, Marte K; Amundsen, Svanstrøm Silja; Helgeland, Hanna; Holm, Kristian; Flåm, Siri Tennebø & Lie, Benedicte Alexandra (2016). Autoimmune risk variants in ERAP2 are associated with gene-expression levels in thymus. Genes and Immunity.  ISSN 1466-4879.  17(7), s 406- 411 . doi: 10.1038/gene.2016.39
• Gustavsen, Marte Wendel; Celius, Elisabeth Gulowsen; Winsvold, Bendik K S; Moen, Stine Marit; Nygaard, Gro Owren; Berg-Hansen, Pål; Lie, Benedicte Alexandra; Zwart, John-Anker & Harbo, Hanne Flinstad (2016). Migraine and frequent tension-type headache are not associated with multiple sclerosis in a Norwegian case-control study. Multiple Sclerosis Journal, Experimental, Translational and Clinical.  ISSN 2055-2173.  2, s 1- 4 . doi: 10.1177/2055217316682976 Fulltekst i vitenarkiv.
• Wang, Yunpeng; Bos, Steffan Daniel; Harbo, Hanne Flinstad; Thompson, Wesley K.; Schork, Andrew J.; Bettella, Francesco; Witoelar, Aree; Lie, Benedicte Alexandra; Li, Wen; McEvoy, Linda K.; Djurovic, Srdjan; Desikan, Rahul S.; Dale, Anders & Andreassen, Ole Andreas (2016). Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors.. Multiple Sclerosis.  ISSN 1352-4585.  22(14), s 1783- 1793 . doi: 10.1177/1352458516635873
• Mæhlen, Marthe Thoresen; Olsen, Inge Christoffer; Kulle Andreassen, Bettina; Viken, Marte K; Jiang, Xia; Alfredsson, Lars; Källberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina A.; Toes, René E.M.; Zhernakova, Alexandra; Gurierrez-Achury, Javier; de Bakker, Paul L. W.; Martin, Javier; Teruel, Maria; Gonzalez-Gay, Miguel A.; Rodríguez-Rodríguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore Kristian & Lie, Benedicte Alexandra (2015). Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  74(4), s 762- 768 . doi: 10.1136/annrheumdis-2013-204173
• Andreassen, Ole Andreas; Desikan, Rahul S.; Wang, Yunpeng; Thompson, Wesley K.; Schork, Andrew J.; Zuber, Verena; Doncheva, Nadezhda T.; Ellinghaus, Eva; Albrecht, Mario; Mattingsdal, Morten; Franke, Andre; Lie, Benedicte Alexandra; Mills, Ian Geoffrey; Aukrust, Pål; McEvoy, Linda K.; Djurovic, Srdjan; Karlsen, Tom Hemming & Dale, Anders (2015). Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms. PLOS ONE.  ISSN 1932-6203.  10:e 0123057(4) . doi: 10.1371/journal.pone.0123057 Fulltekst i vitenarkiv.
• Andreassen, Ole Andreas; Harbo, Hanne Flinstad; Wang, Yunpeng; Thompson, WK; Schork, AJ; Mattingsdal, Morten; Zuber, Verena; Bettella, Franscesco; Ripke, S; Kelsoe, JR; Kendler, KS; O'Donovan, MC; Sklar, P; McEvoy, LK; Desikan, RS; Lie, Benedicte Alexandra; Djurovic, Srdjan & Dale, Anders M. (2015). Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Molecular Psychiatry.  ISSN 1359-4184.  20(2), s 207- 214 . doi: 10.1038/mp.2013.195 Fulltekst i vitenarkiv.
• Bossini-Castillo, Lara; de Kovel, Carolien G.F.; Källberg, Henrik; van't Slot, Ruben; Italiaander, Annet; Coenen, Marieke J.H.; Tak, Paul P.; Posthumus, Marcel D.; Wijmenga, Cisca; Huizinga, Tom W.J.; van der Helm-van Mil, Annette H.M.; Stoeken-Rijsbergen, Gerrie; Rodríguez-Rodríguez, Luis; Balsa, Alejandro; González-Álvaro, Isidoro; González-Gay, Miguel A.; Gómez-Vaquero, Carmen; Franke, Barbara; Vermeulen, Sita H.; van der Horst-Bruinsma, Irene E.; Dijkmans, Ben A.C.; Wolbink, Gerrit Jan; Ophoff, Roel A.; Mæhlen, Marthe Thoresen; van Riel, Piet; Merriman, Marilyn; Klareskog, Lars; Lie, Benedicte Alexandra; Merriman, Tony; Crusius, J. Bart A.; Brouwer, Elisabeth; Martin, Javier; de Vries, Niek; Toes, René E.M.; Padyukov, Leonid & Koeleman, Bobby P.C. (2015). A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  74(e15) . doi: 10.1136/annrheumdis-2013-204591
• Chiaroni-Clarke, Rachel C.; Li, Yun R.; Munro, Jane E.; Chavez, Raul A.; Scurrah, Katrina J.; Pezic, Angela; Akikusa, Jonathan D.; Allen, Roger C.; Piper, Susan E.; Becker, Mara L.; Thompson, Susan D.; Lie, Benedicte Alexandra; Flatø, Berit; Førre, Øystein Thorleiv; Punaro, Marilynn; Wise, Carol; Saffery, Richard; Finkel, Terri H.; Hakonarson, Hakon; Ponsonby, Anne-Louise & Ellis, Justine A. (2015). The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes and Immunity.  ISSN 1466-4879.  16(7), s 495- 498 . doi: 10.1038/gene.2015.32
• Cortes, Adrian; Pulit, Sara L.; Leo, Paul J.; Pointon, Jenny J.; Robinson, Philip C.; Weisman, Michael H.; Ward, Michael; Gensler, Lianne S.; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte Alexandra; Førre, Øystein Thorleiv; Tuomilehto, Jaakko; Laiho, Kari; Bradbury, Linda A.; Elewaut, Dirk; Burgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Haroon, Nigil; Mulero, Juan; Blanco, Francisco J.; González-Gay, Miguel A.; López-Larrea, Carlos; Bowness, Paul; Gaffney, Karl; Gaston, Hill; Gladman, Dafna D.; Rahman, Proton; Maksymowych, Walter P.; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Valle-Oñate, Raphael; Romero-Sánchez, Consuelo; Myrnes, Inger; Pimentel-Santos, Fernando M.; Inman, Robert D.; Martin, Javier; Breban, Maxime; Wordsworth, Bryan Paul; Reveille, John D.; Evans, David M.; de Bakker, Paul I.W. & Brown, Matthew A. (2015). Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nature Communications.  ISSN 2041-1723.  6 . doi: 10.1038/ncomms8146
• Ellis, Justine A.; Scurrah, Katrina J.; Li, Yun R.; Ponsonby, Anne-Louise; Chavez, Raul A.; Pezic, Angela; Dwyer, Terence; Akikusa, Jonathan D.; Allen, Roger C.; Becker, Mara L.; Thompson, Susan D.; Lie, Benedicte Alexandra; Flatø, Berit; Førre, Øystein Thorleiv; Punaro, Marilynn; Wise, Carol; Finkel, Terri H.; Hakonarson, Hakon & Munro, Jane E. (2015). Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis. Journal of Steroid Biochemistry and Molecular Biology.  ISSN 0960-0760.  145, s 113- 120 . doi: 10.1016/j.jsbmb.2014.10.012
• Flåm, Siri Tennebø; Gunnarsson, Ragnar; Garen, Torhild Oddveig; Lie, Benedicte Alexandra & Molberg, Øyvind (2015). The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. Rheumatology.  ISSN 1462-0324.  54(3), s 528- 535 . doi: 10.1093/rheumatology/keu310
• Hov, Johannes Espolin Roksund; Zhong, Huanzi; Qin, Bincai; Anmarkrud, Jarl Andreas; Holm, Kristian; Franke, Andre; Lie, Benedicte Alexandra & Karlsen, Tom Hemming (2015). The influence of the autoimmunity-associated ancestral HLA haplotype AH8.1 on the human gut microbiota: A cross-sectional study. PLOS ONE.  ISSN 1932-6203.  10:e0133804(7) . doi: 10.1371/journal.pone.0133804
• Li, Yun R.; Li, Jin; Zhao, Sihai D.; Bradfield, Jonathan P.; Mentch, Frank D.; Maggadóttir, Sólrún Melkorka; Hou, Cuiping; Abrams, Debra J.; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Glessner, Joseph T.; Li, Dong; Kao, Charlly; Thomas, Kelly A.; Qiu, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Richie, Marylyn D.; Flatø, Berit; Førre, Øystein Thorleiv; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K.; Wilson, David C.; Silverberg, Mark S.; Annese, Vito; Lie, Benedicte Alexandra; Punaro, Marilynn; Dubinsky, Marla C.; Monos, Dimitri S.; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A.; Munro, Jane E.; Sullivan, Kathleen E.; Wise, Carol A.; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F.A.; Orange, Jordan S.; Sleiman, Patrick M.A.; Behrens, Edward M.; Griffiths, Anne M.; Satsangi, Jack; Finkel, Terri H.; Keinan, Alon; Prak, Eline T. Luning; Polychronakos, Constantin; Baldassano, Robert N.; Li, Hongzhe; Keating, Brendan J. & Hakonarson, Hakon (2015). Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nature Medicine.  ISSN 1078-8956.  21(9), s 1018- 1027 . doi: 10.1038/nm.3933
• Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede; Steel, Laura; Kobie, Julie; Abrams, Debra J.; Mentch, Frank D.; Glessner, Joseph T.; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Li, Dong; Maggadóttir, Sólrún Melkorka; Thomas, Kelly A.; Qui, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Flatø, Berit; Førre, Øystein Thorleiv; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L.; Latiano, Anna; Perez, Elena; Resnick, Elena; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Silverberg, Mark S.; Lie, Benedicte Alexandra; Punaro, Marilynn; Russell, Richard K.; Wilson, David C.; Dubinsky, Marla C.; Monos, Dimitri S.; Annese, Vito; Munro, Jane E.; Wise, Carol; Chapel, Helen; Cunningham-Rundles, Charlotte; Orange, Jordan S.; Behrens, Edward M.; Sullivan, Kathleen E.; Kugathasan, Subra; Griffiths, Anne M.; Satsangi, Jack; Grant, Struan F.A.; Sleiman, Patrick M.A.; Finkel, Terri H.; Polychronakos, Constantin; Baldassano, Robert N.; Luning Prak, Eline T.; Ellis, Justine A.; Li, Hongzhe; Keating, Brendan J. & Hakonarson, Hakon (2015). Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nature Communications.  ISSN 2041-1723.  6:8442 . doi: 10.1038/ncomms9442
• Omair, Ahmad; Mannion, Anne F.; Holden, Marit; Fairbank, Jeremy; Lie, Benedicte Alexandra; Hägg, Olle; Fritzell, Peter & Brox, Jens Ivar (2015). Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with baseline disability but not long-term treatment outcome in patients with chronic low back pain. European spine journal.  ISSN 0940-6719.  24(11), s 2425- 2431 . doi: 10.1007/s00586-015-3866-5 Vis sammendrag

  Purpose: To examine the association between COMT and OPRM1 gene polymorphisms and pain and disability at baseline and long-term follow-up in patients treated for chronic low back pain (LBP). Methods: 371 of 767 unrelated European patients recruited from four randomised trials underwent genetic analyses at mean 11.4 years follow-up. 274 patients had fusion and 97 had non-operative treatment. Association analyses included disability, pain, five single nucleotide polymorphisms (SNPs) in the COMT gene, and one SNP in the OPRM1 gene. Analyses were adjusted for age, gender, smoking, analgesics and treatment. Results: Disability at baseline was significantly associated with COMT SNPs rs4818 (p = 0.02), rs6269 (p = 0.007), rs4633 (p = 0.04) rs2075507 (p = 0.009), two haplotypes (p < 0.002), age, gender and smoking (p ≤ 0.002). No significant associations with clinical variables were observed for OPRM1, or for COMT at long-term follow-up. Conclusions: Results suggest that genetic factors are partly responsible for the variation in disability levels in patients presenting with chronic LBP being considered for surgery; in contrast, genetics has no influence on the long-term outcome of treatment.

• Seldin, Michael F.; Alkhairy, Omar K; Lee, Annette T.; Lamb, Janine; Sussman, Jon; Pirskanen-Matell, Ritva; Piehl, Fredrik; Verschuuren, Jan J. G. M; Kostera-Pruszczyk, Anna; Szczudlik, Piotr; McKee, David; Maniaol, Angelina; Harbo, Hanne Flinstad; Lie, Benedicte Alexandra; Melms, Arthur; Garchon, Henri-Jean; Willcox, Nicholas; Gregersen, Peter K & Hammarstrom, Lennart (2015). Genome-wide association study of late-onset myasthenia gravis: Confirmation of TNFRSF11A and identification of ZBTB10 and three distinct HLA associations. Molecular medicine (Cambridge, Mass. Print).  ISSN 1076-1551.  21, s 769- 781 . doi: 10.2119/molmed.2015.00232 Vis sammendrag

  To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti–acetylcholine receptor [AChR] antibody positive; onset age ≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10–7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10–10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10–6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 versus ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10–12) versus 2.82 in EOMG (P = 3.86 × 10–45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG.

• Amundsen, Svanstrøm Silja; Viken, Marte K; Sollid, Ludvig Magne & Lie, Benedicte Alexandra (2014). Coeliac disease-associated polymorphisms influence thymic gene expression. Genes and Immunity.  ISSN 1466-4879.  15(6), s 355- 360 . doi: 10.1038/gene.2014.26
• Andersen, Ina Marie Riise; Tengesdal, Guro; Lie, Benedicte Alexandra; Boberg, Kirsten Muri; Karlsen, Tom Hemming & Hov, Johannes Espolin Roksund (2014). Effects of Coffee Consumption, Smoking, and Hormones on Risk for Primary Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology.  ISSN 1542-3565.  12(6), s 1019- 1028 . doi: 10.1016/j.cgh.2013.09.024
• Avidan, Nili; Panse, Rozen Le; Harbo, Hanne Flinstad; Bernasconi, Pia; Poulas, Konstantinos; Ginzburg, Elizabeta; Cavalcante, Paola; Colleoni, Lara; Baggi, Fulvio; Antozzi, Carlo; Truffault, Frederique; Horn-Saban, Shirley; Poschel, Simone; Zagoriti, Zoi; Maniaol, Angelina; Lie, Benedicte Alexandra; Bernard, Isabelle; Saoudi, Abdelhadi; Illes, Zsolt; Pons, Carlos Casasnovas; Melms, Arthur; Tzartos, Socrates; Willcox, Nicholas; Kostera-Pruszczyk, Anna; Tallaksen, Chantal; Mantegazza, Renato; Berrih-Aknin, S. & Miller, Ariel (2014). VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis. Annals of clinical and translational neurology.  ISSN 2328-9503.  1(5), s 329- 339 . doi: 10.1002/acn3.51
• Gustavsen, Marte Wendel; Page, Christian; Moen, Stine Marit; Bjølgerud, Anja; Berg-Hansen, Pål; Nygaard, Gro Owren; Sandvik, Leiv; Lie, Benedicte Alexandra; Celius, Elisabeth Gulowsen & Harbo, Hanne Flinstad (2014). Environmental exposures and the risk of multiple sclerosis investigated in a Norwegian case-control study. BMC Neurology.  ISSN 1471-2377.  14(1) . doi: 10.1186/s12883-014-0196-x Fulltekst i vitenarkiv.
• Gustavsen, Marte Wendel; Viken, Marte K; Celius, Elisabeth Gulowsen; Berge, Tone; Mero, Inger-Lise; Berg-Hansen, Pål; Aarseth, Jan Harald; Myhr, Kjell-Morten; Søndergaard, Helle Bach; Sellebjerg, Finn; Oturai, Annette Bang; Hillert, Jan; Alfredsson, Lars; Olsson, Tomas; Kockum, Ingrid; Lie, Benedicte Alexandra & Harbo, Hanne Flinstad (2014). Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general. Journal of Neuroimmunology.  ISSN 0165-5728.  274(1-2), s 174- 179 . doi: 10.1016/j.jneuroim.2014.06.024
• Moreno-Mayar, J. Victor; Rasmussen, Simon; Seguin-Orlando, Andaine; Rasmussen, Morten; Liang, Mason; Flåm, Siri Tennebø; Lie, Benedicte Alexandra; Gilfillan, Gregor Duncan; Nielsen, Rasmus; Thorsby, Erik; Willerslev, Eske & Malaspinas, Anna-Sapfo (2014). Genome-wide ancestry patterns in rapanui suggest pre-european admixture with native americans. Current Biology.  ISSN 0960-9822.  24(21), s 2518- 2525 . doi: 10.1016/j.cub.2014.09.057
• Næss, Sigrid; Björnsson, Einar; Anmarkrud, Jarl Andreas; Al Mamari, Said; Juran, Brian D.; Lazaridis, Konstantinos N.; Chapman, Roger W.; Annika, Bergquist; Melum, Espen; Marsh, Steven G.E.; Schrumpf, Erik; Lie, Benedicte Alexandra; Boberg, Kirsten Muri; Karlsen, Tom Hemming & Hov, Johannes Espolin Roksund (2014). Small duct primary sclerosing cholangitis without inflammatory bowel disease is genetically different from large duct disease. Liver international (Print).  ISSN 1478-3223.  34(10), s 1488- 1495 . doi: 10.1111/liv.12492
• Næss, Sigrid; Lie, Benedicte Alexandra; Melum, Espen; Olsson, Marita; Hov, Johannes Espolin Roksund; Croucher, PJP; Hampe, Jochen; Thorsby, Erik; Bergquist, Annika; Traherne, James A.; Schrumpf, Erik; Boberg, Kirsten Muri; Schreiber, Stefan; Franke, Andre & Karlsen, Tom Hemming (2014). Refinement of the MHC risk map in a Scandinavian primary sclerosing cholangitis population. PLOS ONE.  ISSN 1932-6203.  9:e0114486(12) . doi: 10.1371/journal.pone.0114486
• Tinholt, Mari; Viken, Marte K; Dahm, Anders Erik A; Vollan, Hans Kristian Moen; Sahlberg, Kristine Kleivi; Garred, Øystein; Børresen-Dale, Anne-Lise; Jacobsen, Anne Flem; Kristensen, Vessela N.; Bukholm, Ida Rashida Khan; Kåresen, Rolf; Schlichting, Ellen; Skretting, Grethe; Lie, Benedicte Alexandra; Sandset, Per Morten & Iversen, Nina (2014). Increased coagulation activity and genetic polymorphisms in the F5, F10 and EPCR genes are associated with breast cancer: a case-control study. BMC Cancer.  ISSN 1471-2407.  14 . doi: 10.1186/1471-2407-14-845
• Beecham, Ashley H.; Patsopoulos, NA; Xifara, DK; Davis, MF; Kemppinen, A; Cotsapas, C; Shah, TS; Spencer, C; Booth, D; Goris, A; Oturai, A; Saarela, J; Fontaine, B; Hemmer, B; Martin, C; Zipp, F; D'Alfonso, S; Martinelli-Boneschi, F; Taylor, B; Harbo, Hanne Flinstad; Kockum, I; Hillert, J; Olsson, T; Ban, M; Oksenberg, JR; Hintzen, R; Barcellos, LF; Agliardi, C; Alfredsson, L; Alizadeh, M; Anderson, C; Andrews, R; Sondergaard, HB; Baker, A; Band, G; Baranzini, SE; Barizzone, N; Barrett, J; Bellenguez, C; Bergamaschi, L; Bernardinelli, L; Berthele, A; Biberacher, V; Binder, TMC; Blackburn, H; Bomfim, IL; Brambilla, P; Broadley, S; Brochet, B; Brundin, L; Buck, D; Butzkueven, H; Caillier, SJ; Camu, W; Carpentier, W; Cavalla, P; Celius, Elisabeth Gulowsen; Coman, I; Comi, G; Corrado, L; Cosemans, L; Cournu-Rebeix, I; Cree, BAC; Cusi, D; Damotte, V; Defer, G; Delgado, SR; Deloukas, P; di Sapio, A; Dilthey, AT; Donnelly, P; Dubois, B; Duddy, M; Edkins, S; Elovaara, I; Esposito, F; Evangelou, N; Fiddes, B; Field, J; Franke, A; Freeman, C; Frohlich, IY; Galimberti, D; Gieger, C; Gourraud, PA; Graetz, C; Graham, A; Grummel, V; Guaschino, C; Hadjixenofontos, A; Hakonarson, H; Halfpenny, C; Hall, G; Hall, P; Hamsten, A; Harley, J; Harrower, T; Hawkins, C; Hellenthal, G; Hillier, C; Hobart, J; Hoshi, M; Hunt, SE; Jagodic, M; Jelcic, I; Jochim, A; Kendall, B; Kermode, A; Kilpatrick, T; Koivisto, K; Konidari, I; Korn, T; Kronsbein, H; Langford, C; Larsson, M; Lathrop, M; Lebrun-Frenay, C; Lechner-Scott, J; Lee, MH; Leone, MA; Leppa, V; Liberatore, G; Lie, Benedicte Alexandra; Lill, CM; Linden, M; Link, J; Luessi, F; Lycke, J; Macciardi, F; Mannisto, S; Manrique, CP; Martin, R; Martinelli, V; Mason, D; Mazibrada, G; McCabe, C; Mero, Inger-Lise; Mescheriakova, J; Moutsianas, L; Myhr, Kjell-Morten; Nagels, G; Nicholas, R; Nilsson, P; Piehl, F; Pirinen, M; Price, SE; Quach, H; Reunanen, M; Robberecht, W; Robertson, NP; Rodegher, M; Rog, D; Salvetti, M; Schnetz-Boutaud, NC; Sellebjerg, F; Selter, RC; Schaefer, C; Shaunak, S; Shen, L; Shields, S; Siffrin, V; Slee, M; Sorensen, PS; Sorosina, M; Sospedra, M; Spurkland, Anne; Strange, A; Sundqvist, E; Thijs, V; Thorpe, J; Ticca, A; Tienari, P; van Duijn, C; Visser, EM; Vucic, S; Westerlind, H; Wiley, JS; Wilkins, A; Wilson, JF; Winkelmann, J; Zajicek, J; Zindler, E; Haines, JL; Pericak-Vance, MA; Ivinson, AJ; Stewart, G; Hafler, D; Hauser, SL; Compston, A; McVean, G; De Jager, P; Sawcer, SJ & McCauley, JL (2013). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics.  ISSN 1061-4036.  45(11), s 1353- 1360 . doi: 10.1038/ng.2770
• Mæhlen, Marthe Thoresen; Provan, Sella Aarrestad; de Rooy, Diederik P.C.; van der Helm-van Mil, Annette H.M.; Krabben, Annemarie; Saxne, Tore; Lindqvist, Elisabet; Semb, Anne Grete; Uhlig, Till; Heijde, Desirée van der; Mero, Inger-Lise; Olsen, Inge Christoffer; Kvien, Tore Kristian & Lie, Benedicte Alexandra (2013). Associations between APOE Genotypes and Disease Susceptibility, Joint Damage and Lipid Levels in Patients with Rheumatoid Arthritis. PLOS ONE.  ISSN 1932-6203.  8(4) . doi: 10.1371/journal.pone.0060970
• Cortes, Adrian; Hadler, Johanna; Pointon, JP; Robinson, Philip; Karaderi, Kudce; Leo, Paul; Cremin, Katie; Pryce, Karena; Harris, Jessica; Lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Xiaodong, Zhou; Garchon, Henri-Jean; Karaderi, T; Nossent, Johannes C; Lie, Benedicte Alexandra; Førre, Øystein Thorleiv; Tuomilehto, Jaako; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Bradbury, Linda A; Elewaut, Dirk; Bourgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Kenna, Tony J; Haroon, Nigel; Ferreira, Manuel A.; Yang, J; Mulero, Juan; Fernandez-Sueiro, Jose Luis; Gonzalez-Gay, Miguel A.; Lopez-Larrea, Carlos; Deloukas, Panos; Donelly, Peter; Bowness, Paul; Gafney, Karl; Gaston, Hill; Gladman, Dafna D.; Rahman, Proton; Maksymowych, Walter P.; Xu, Huji; Crusius, J Bart A; Horst-Bruinsma, Irene E van der; Chou, CT; Valle-Onate, R; Romero-Sanchez, C; Hansen, Inger Myrnes; Pimentel-Santos, FM; Inman, Robert D; Videm, Vibeke; Martin, J; Breban, Maxime; Reveille, John D; Evans, DM; Kim, Tae-Hwan; Wordsworth, Bryan Paul; Brown, Matthew & Chiocchia, Gilles (2013). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature Genetics.  ISSN 1061-4036.  45(7), s 730- 738 . doi: 10.1038/ng.2667
• Elbarbary, Nancy S.; Tjora, Erling; Molnes, Janne; Lie, Benedicte Alexandra; Habib, Mohammad A.; Salem, Mona A. & Njølstad, Pål Rasmus (2013). An Egyptian family with H syndrome due to a novel mutation in SLC29A3 illustrating overlapping features with pigmented hypertrichotic dermatosis with insulin-dependent diabetes and Faisalabad histiocytosis. Pediatric Diabetes.  ISSN 1399-543X.  14(6), s 466- 472 . doi: 10.1111/j.1399-5448.2012.00925.x
• Leikfoss, Ingvild Sørum; Mero, Inger-Lise; Dahle, Maria Krudtaa; Lie, Benedicte Alexandra; Harbo, Hanne Flinstad; Spurkland, Anne & Berge, Tone (2013). Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus. Genes and Immunity.  ISSN 1466-4879.  14(1), s 62- 66 . doi: 10.1038/gene.2012.52
• Mero, Inger-Lise; Gustavsen, Marte Wendel; Sæther, Hanne Skarpodde; Flåm, Siri Tennebø; Berg-Hansen, Pål; Søndergaard, Helle Bach; Jensen, Poul Erik Hyldgaard; Berge, Tone; Bjølgerud, Anja; Muggerud, Aslaug; Aarseth, Jan Harald; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen; Sellebjerg, Finn; Hillert, Jan; Alfredsson, Lars; Olsson, Tomas; Oturai, Annette Bang; Kockum, Ingrid; Lie, Benedicte Alexandra; Kulle, Bettina & Harbo, Hanne Flinstad (2013). Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles. PLOS ONE.  ISSN 1932-6203.  8(3) . doi: 10.1371/journal.pone.0058352
• Namløs Nordang, Gry Beate; Flåm, Siri Tennebø; Mæhlen, Marthe Thoresen; Kvien, Tore Kristian; Viken, Marte K & Lie, Benedicte Alexandra (2013). HLA-C alleles confer risk for anti-citrullinated peptide antibody-positive rheumatoid arthritis independent of HLA-DRB1 alleles. Rheumatology.  ISSN 1462-0324.  52(11), s 1973- 1982 . doi: 10.1093/rheumatology/ket252
• Omair, Ahmad; Holden, Marit; Lie, Benedicte Alexandra; Reikerås, Olav & Brox, Jens Ivar (2013). Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: a prospective genetic association study. BMC Musculoskeletal Disorders.  ISSN 1471-2474.  14(105) . doi: 10.1186/1471-2474-14-105 Vis sammendrag

  Background: Inflammatory and matrix degrading gene variants have been reported to be associated with disc degeneration. Some of these variants also modulate peripheral pain. This study examines the association of these genetic variants with radiographic lumbar disc degeneration and changes in pain and disability at long-term after surgical and cognitive behavioural management. Methods: 93 unrelated patients with chronic low back pain (CLBP) for duration of >1 year and lumbar disc degeneration were treated with lumbar fusion or cognitive intervention and exercises. Standardised questionnaires included the Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for CLBP, were filled in by patients both at baseline and at 9 years follow-up. Degenerative changes at baseline Magnetic Resonance Imaging and Computed Tomography scans, were graded as moderate and severe (N=79). Yield and quality of blood and saliva DNA was assessed by nano drop spectrophotometry. Eight SNPs in 5 inflammatory and matrix degrading genes were successfully genotyped. Single marker and haplotype association with severity of degeneration, number of discs involved, changes in ODI and VAS CLBP, was done using Haploview, linear regression and R-package Haplostats. Results: Association analysis of individual SNPs revealed association of IL18RAP polymorphism rs1420100 with severe degeneration (p = 0.05) and more than one degenerated disc (p = 0.02). From the same gene two SNPs, rs917997 and rs1420106, were found to be in strong linkage disequilibrium (LD) and were associated with post treatment improvement in disability (p = 0.02). Haplotype association analysis of 5 SNPs spanning across IL18RAP, IL18R1 and IL1A genes revealed significant associations with improvement in disability (p=0.02) and reduction in pain (p=0.04). An association was found between MMP3 polymorphism rs72520913 and improvement in pain (p = 0.03) and with severe degeneration (p = 0.006). Conclusions: The findings of the current study suggest a role of variation at inflammatory and matrix degrading genes with severity of lumbar disc degeneration, pain and disability.

• Serrano, A.; Márquez, Arturo; Mackie, SL; Carmona, Francisco David; Solans, R.; Miranda-Filloy, JA; Hernandez-Rodriguez, J.; Cid, MC; Castaneda, S.; Morado, IC; Narváez, Javier; Blanco, R.; Sopena, B.; Garcia-Villanueva, MJ; Monfort, J.; Ortego-Centeno, N; Unzurrunzaga, A.; Mari-Alfonso, B.; Sanchez-Martin, J.; de Miguel, E.; Magro, C.; Raya, E; Braun, N; Latus, J.; Molberg, Øyvind; Lie, Benedicte Alexandra; Moosig, F.; Witte, T; Morgan, AW; Gonzalez-Gay, Miguel A. & Martin, J. (2013). Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  72(11), s 1882- 1886 . doi: 10.1136/annrheumdis-2013-203641
• Teruel, Maria; McKinney, Cushla; Balsa, Alejandro; Pascual-Salcedo, Dora; Rodríguez-Rodríguez, Luis; Ortiz, Ana M.; Gómez-Vaquero, Carmen; Gonzalez-Gay, Miguel A.; Smith, Malcolm; Witte, Torsten; Merriman, Tony; Lie, Benedicte Alexandra & Martin, Javier (2013). Association of CD247 polymorphisms with rheumatoid athritis: a replication study and a meta-analysis. PLOS ONE.  ISSN 1932-6203.  8(7:e68295) . doi: 10.1371/journal.pone.0068295
• Vang, Torkel; Landskron, Johannes; Viken, Marte K; Oberprieler, Nikolaus; Torgersen, Knut Martin; Mustelin, Tomas; Tasken, Kjetil; Tautz, Lutz; Rickert, Robert C. & Lie, Benedicte Alexandra (2013). The autoimmune-predisposing variant of lymphoid tyrosine phosphatase favors T helper 1 responses. Human Immunology.  ISSN 0198-8859.  74(5), s 574- 585 . doi: 10.1016/j.humimm.2012.12.017
• Daha, Nina A.; Lie, Benedicte Alexandra; Trouw, Leendert A.; Stoeken, Gerrie; Schonkeren, Joris J.M.; Ding, Bo; Kvien, Tore Kristian; Schilham, Marco W.; Padyukov, Leonid; Huizinga, Tom W.J. & Toes, René E.M. (2012). Novel genetic association of the VTCN1 region with rheumatoid arthritis. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  71(4), s 567- 571 . doi: 10.1136/annrheumdis-2011-200574
• Eike, Morten Christoph; Skinningsrud, Beate; Ronninger, Marcus; Stormyr, Alice; Kvien, Tore Kristian; Joner, Geir; Njølstad, Pål Rasmus; Førre, Øystein Thorleiv; Flatø, Berit; Alfredsson, Lars; Padyukov, Leonid; Undlien, Dag Erik & Lie, Benedicte Alexandra (2012). CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations. Genes and Immunity.  ISSN 1466-4879.  13(5), s 431- 436 . doi: 10.1038/gene.2012.11 Vis sammendrag

  Expression of the major autoimmune risk loci DRB1 and DQB1 is regulated by the class II MHC (major histocompatibility complex) transactivator (CIITA), making the CIITA gene a strong autoimmune risk locus candidate. A CIITA promoter single-nucleotide polymorphism (SNP), rs3087456 (-168 A/G), has indeed been associated with several autoimmune diseases, including rheumatoid arthritis (RA). Recently, an intronic SNP rs8048002 has been suggested as a better susceptibility marker in Addison's disease. Therefore, we tested both SNPs in a panel of autoimmune diseases, consisting of Norwegian patients with RA (n=819), juvenile idiopathic arthritis (JIA; n=524), or type 1 diabetes (T1D; n=1211), and 2149 controls. We also included an independent Swedish RA cohort (n=2503) and controls (n=1416). Both rs3087456 and rs8048002 were significantly associated with RA (combined Norwegian and Swedish patients P(corrected)=0.012 and P(corrected)=0.0016, respectively), but not with JIA or T1D. Meta-analysis of 16 RA cohorts confirmed rs3087456 with only marginal significance (P=0.016). However, results were stronger in the Scandinavian subgroup (4 cohorts, P=3.8 × 10(-4)), indicating a population-dependent effect. A similar pattern was observed in a meta-analysis of rs8048002. Our results support involvement of CIITA in RA, but imply that this is population dependent and that the aetiological variant is yet to be discovered.

• Gregersen, Peter K.; Kosoy, Roman; Lee, Annette T.; Lamb, Janine; Sussman, Jon; McKee, David; Simpfendorfer, Kim R.; Pirskanen-Matell, Ritva; Piehl, Frederik; Pan-Hammarstrom, Qiang; Verschuuren, Jan J. G. M; Titulaer, Maarten J.; Niks, Erik N.; Marx, Alexander; Ströbel, Philipp; Tackenberg, Björn; Pütz, Michael; Maniaol, Angelina; Elsais, Ahmed; Tallaksen, Chantal; Harbo, Hanne Flinstad; Lie, Benedicte Alexandra; Raychaudhuri, Soumya; de Bakker, Paul L. W.; Melms, Arthur; Garchon, Henri-Jean; Willcox, Nicholas; Hammarstrom, Lennart & Seldin, Michael F. (2012). Risk for Myasthenia Gravis Maps to a 151Pro!Ala Change in TNIP1 and to Human Leukocyte Antigen-B*08. Annals of Neurology.  ISSN 0364-5134.  72(6), s 927- 935 . doi: 10.1002/ana.23691
• Link, Jenny; Kockum, Ingrid; Lorentzen, Åslaug Rudjord; Lie, Benedicte Alexandra; Celius, Elisabeth Gulowsen; Westerlind, Helga; Schaffer, Marie; Alfredsson, Lars; Olsson, Tomas; Brynedal, Boel; Harbo, Hanne Flinstad & Hillert, Jan (2012). Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis. PLOS ONE.  ISSN 1932-6203.  7(5:e36779) . doi: 10.1371/journal.pone.0036779
• Maniaol, Angelina; Elsais, Ahmed; Lorentzen, Åslaug Rudjord; Owe, Jone Furulund; Viken, Marte K; Sæther, Hanne Skarpodde; Flåm, Siri Tennebø; Bråthen, Geir; Kampman, Margitta Theodora; Midgard, Rune; Christensen, Marte; Rognerud, Anna Kaja; Kerty, Emilia; Gilhus, Nils Erik; Tallaksen, Chantal; Lie, Benedicte Alexandra & Harbo, Hanne Flinstad (2012). Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population. PLOS ONE.  ISSN 1932-6203.  7(5) . doi: 10.1371/journal.pone.0036603 Fulltekst i vitenarkiv.
• Mero, Inger-Lise; SMESTAD, CATHRINE; Lie, Benedicte Alexandra; Lorentzen, Åslaug Rudjord; Sandvik, Leiv; Landrø, Nils Inge; Aarseth, Jan Harald; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen & Harbo, Hanne Flinstad (2012). Polymorphisms of the BDNF gene show neither association with multiple sclerosis susceptibility nor clinical course. Journal of Neuroimmunology.  ISSN 0165-5728.  244(1-2), s 107- 110 . doi: 10.1016/j.jneuroim.2012.01.011
• Namløs, Gry Beate; Carpenter, Daniela; Viken, Marte K; Kvien, Tore Kristian; Armour, John & Lie, Benedicte Alexandra (2012). Association analysis of the CCL3L1 copy number locus by paralogue ratio test in Norwegian rheumatoid arthritis patients and healthy controls. Genes and Immunity.  ISSN 1466-4879.  13(7), s 579- 582 . doi: 10.1038/gene.2012.30
• Nordang, Gry Beate Namløs; Viken, Marte K; Amundsen, Svanstrøm Silja; Sanchez, Elena S.; Flatø, Berit; Førre, Øystein Thorleiv; Martin, Javier; Kvien, Tore Kristian & Lie, Benedicte Alexandra (2012). Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts. Rheumatology.  ISSN 1462-0324.  51(4), s 619- 626 . doi: 10.1093/rheumatology/ker364
• Omair, Ahmad; Lie, Benedicte Alexandra; Reikerås, Olav; Holden, Marit & Brox, Jens Ivar (2012). Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study. BMC Musculoskeletal Disorders.  ISSN 1471-2474.  13 . doi: 10.1186/1471-2474-13-76 Vis sammendrag

  Background Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7–11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise. Methods 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7–11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well as haplotype association with change in ODI and VAS LBP, were analyzed using Haploview, linear regression and R-package Haplostats. P-values were not formally corrected for multiple testing as this was an explorative study. Results Association analysis of individual SNPs adjusted for covariates revealed association of rs4633 and rs4680 with post treatment improvement in VAS LBP (p = 0.02, mean difference (β) = 13.5 and p = 0.02, β = 14.2 respectively). SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong linkage disequilibrium (LD). A significant association was found with covariates, analgesics (p = 0.001, β = 18.6); anxiety and depression (p = 0.008, β = 15.4) and age (p = 0.03, mean difference per year (β) = 0.7) at follow-up. There was a tendency for better improvement among heterozygous patients compared to the homozygous. No association was observed for the analysis of the common haplotypes, these SNPs were situated on. Conclusions Results suggest an influence of genetic variants of COMT gene in describing the variation in pain after treatment for low back pain. Replication in large samples with testing for other pain related genes is warranted.

• Ronninger, Marcus; Seddighzadeh, Maria; Eike, Morten Christoph; Plant, Darren; Daha, Nina A.; Skinningsrud, Beate; Worthington, Jane; Kvien, Tore Kristian; Toes, René E.M.; Lie, Benedicte Alexandra; Alfredsson, Lars & Padyukov, Leonid (2012). Interaction Analysis between HLA-DRB1 Shared Epitope Alleles and MHC Class II Transactivator CIITA Gene with Regard to Risk of Rheumatoid Arthritis. PLOS ONE.  ISSN 1932-6203.  7(3), s e32861 . doi: 10.1371/journal.pone.0032861 Vis sammendrag

  HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases. We wanted to explore whether the risk variant rs3087456 in the CIITA gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA. We tested this hypothesis in a case-control study with 11767 individuals from four European Caucasian populations (6649 RA cases and 5118 controls). We found no significant additive interaction for risk alleles among Swedish Caucasians with RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: −0.2–0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA) presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: −0.05–0.6, ACPA negative: n = 2268, AP = −0.2, 95%CI: −1.0–0.6). We further found no significant interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from British, Dutch and Norwegian populations also indicated an absence of significant interaction between genetic variants in CIITA and SE alleles with regard to RA risk. Our data suggest that risk from the CIITA locus is independent of the major risk for RA from HLA-DRB1 SE alleles, given that no significant interaction between rs3087456 and SE alleles was observed. Since a biological link between products of these genes is evident, the genetic contribution from CIITA and class II antigens in the autoimmune process may involve additional unidentified factors.

• Rønningen, Kjersti Skjold; Yap, Soen Eng; Brandal, Kristin; Stormyr, Alice; Lie, Benedicte Alexandra; Rasmussen, T.; Stray-Pedersen, Babill & Akselsen, Hanne Elisabeth (2012). HLA-DRB1,-DQA1 and-DQB1 Alleles and Haplotypes in First-Generation Pakistani Immigrants in Norway. Scandinavian Journal of Immunology.  ISSN 0300-9475.  75(4), s 426- 430 . doi: 10.1111/j.1365-3083.2011.02669.x
• Sanchez-Mazas, Alicia; Vidan-Jeras, Blanka; Nunes, José Manuel de Abreu; Fischer, Gabriele; Little, Ann-Margaret; Bekmane, Una; Buhler, Stéphane; Buus, Søren; Claas, Frans H.J.; Dormoy, Anne; Dubois, Valerie; Eglite, Eliza; Eliaou, Jean-Francois; Gonzalez-Galarza, Faviel; Grubic, Zorana; Ivanova, Milena; Lie, Benedicte Alexandra; Ligeiro, Dário; Lokki, Marja-Liisa; Martins da Silva, Berta; Martorell, Jaime; Mendonça, Diogo de; Middleton, Derek; Voniatis, D. Papioannou; Papasteriades, Chryssa; Poli, Francesca; Riccio, Maria Elena; Spyropoulou Vlachou, Maria; Sulcebe, Genc; Tonks, Susan; Nevessignsky, Michel Toungouz; Vangenot, Christelle; van Walraven, Anne-Marie & Tiercy, Jean-Marie (2012). Strategies to work with HLA data in human populations for histocompatibility, clinical transplantation, epidemiology and population genetics: HLA-NET methodological recommendations. International Journal of Immunogenetics.  ISSN 1744-3121.  39(6), s 459- 476 . doi: 10.1111/j.1744-313X.2012.01113.x
• Vang, Torkel; Liu, Wallace H.; Delacroix, Laurence; Wu, Shuangding; Vasile, Stefan; Dahl, Russell; Yang, Li; Musumeci, Lucia; Francis, Dana; Landskron, Johannes; Tasken, Kjetil; Tremblay, Michel L.; Lie, Benedicte Alexandra; Page, Rebecca; Mustelin, Tomas; Rahmouni, Souad; Rickert, Robert C. & Tautz, Lutz (2012). LYP inhibits T-cell activation when dissociated from CSK. Nature Chemical Biology.  ISSN 1552-4450.  8(5), s 437- 446 . doi: 10.1038/NCHEMBIO.916
• Scherer, Hans Ulrich; van der Woude, Diane; Willemze, Annemiek; Trouw, Leendert A.; Knevel, Rachel; Syversen, Silje Watterdal; van der Linden, Michael P.M.; Lie, Benedicte Alexandra; Huizinga, Tom W.J.; van der Heijde, Desirée; van der Helm-van Mil, Annette H.M.; Kvien, Tore Kristian & Toes, René E.M. (2011). Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  70(8), s 1461- 1464 . doi: 10.1136/ard.2010.146506
• Bossini-Castillo, Lara; Broen, Jasper C.A.; Simeon, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Ortego-Centeno, Norberto; Espinosa, Gerard; Carreira, Patricia; Camps, Maria Teresa; Navarrete, Nuria; Gonzalez-Escribano, Maria F.; Vicente-Rabaneda, Esther; Rodriguez, Luis; Tolosa, Carlos; Roman-Ivorra, Jose A.; Gomez-Gracia, Inmaculada; Garcia-Hernandez, Francisco J.; Castellvi, Ivan; Gallego, Maria; Fernandez-Nebro, Antonio; Garcia-Portales, Rosa; Egurbide, Maria Victoria; Fonollosa, Vicente; de la Pena, Paloma Garcia; Pros, Ana; Gonzalez-Gay, Miguel A.; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Coenen, Marieke J.H.; Koeleman, Bobby P.; Houssiau, Frederic; Smith, Vanessa; de Keyser, Filip; Westhovens, Rene; De Langhe, Ellen; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Chee, Meng May; Madhok, Rajan; Shiels, Paul; Fonseca, Carmen; Denton, Christopher; Claes, Kathleen; Padykov, Leonid; Nordin, Annika; Palm, Øyvind; Lie, Benedicte Alexandra; Airo, Paolo; Scorza, Raffaella; van Laar, Jacob M.; Hunzelmann, Nicolas; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Radstake, Timothy R.D.J.; Martin, Javier & Rueda, Blanca (2011). A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  70(4), s 638- 641 . doi: 10.1136/ard.2010.141838
• Eerligh, P.; Koeleman, B.P.C.; Lie, Benedicte Alexandra; Roep, B.O. & Thorsby, Erik (2011). No extreme genetic risk for type 1 diabetes among DR3/4-DQ8 siblings sharing both extended HLA haplotypes with their diabetic proband. Tissue Antigens.  ISSN 0001-2815.  77(4), s 338- 340 . doi: 10.1111/j.1399-0039.2011.01636.x

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• Gustavsen, Marte Wendel; Celius, Elisabeth Gulowsen; Moen, Stine Marit; Bjølgerud, Anja; Berg-Hansen, Pål; Nygaard, Gro Owren; Sandvik, Leiv; Lie, Benedicte Alexandra & Harbo, Hanne Flinstad (2015). No association between multiple sclerosis and periodontitis after adjusting for smoking habits. European Journal of Neurology.  ISSN 1351-5101.  22(3), s 588- 590 . doi: 10.1111/ene.12520
• Robinson, Philip C.; Costello, Mary-Ellen; Leo, Paul; Bradbury, Linda A.; Hollis, Kelly; Cortes, Adrian; Lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte Alexandra; Førre, Øystein Thorleiv; Tuomilehto, Jaakko; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Elewaut, Dirk; Burgos-Vargas, Ruben; Gensler, Lianne S.; Stebbings, Simon; Haroon, Nigil; Mulero, Juan; Fernandez-Sueiro, Jose Luis; González-Gay, Miguel A.; Lopez-Larrea, Carlos; Bowness, Paul; Gafney, Karl; Gaston, John S. Hill; Gladman, Dafna D.; Rahman, Proton; Maksymowych, Walter P.; Xu, Huji; Van Der Horst-Bruinsma, Irene E.; Chou, Chung-Tei; Valle-Oñate, Raphael; Romero-Sánchez, María Consuelo; Myrnes, Inger; Pimentel-Santos, Fernando M.; Inman, Robert D.; Martin, Javier; Breban, Maxime; Evans, David; Reveille, John D.; Kim, Tae-Hwan; Wordsworth, B. Paul & Brown, Matthew A. (2015). ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  74(8), s 1627- 1629 . doi: 10.1136/annrheumdis-2015-207416
• Sanchez-Mazas, Alicia; Buhler, Stéphane; Bekmane, Uma; Buus, Søren; Claas, Frans H.J.; Dormoy, Anne; Dubois, Valerie; Eberhard, Hans-Peter; Eglite, Jelena; Eliaou, Jean-Francois; Fischer, Gottfried F.; Gonzalez-Galarza, Faviel; Grubic, Zorana; Ivanova, Milena; Lie, Benedicte Alexandra; Ligeiro, Dário; Little, Ann-Margaret; Lokki, Marja-Liisa; Marsh, Stephen; da Silva, Berta Martins; Martorell, Jaume; Mendona, Denisa; Middleton, Derek; Mueller, Carlheinz R.; Voniatis, Constantia Papaioannou; Papasteriades, Chryssa; Poli, Francesca; Riccio, ME; Spyropoulou-Vlachou, Maria; Sulcebe, Genc; Tiercy, Jean-Marie; Tonks, Susan; Tordai, Attila; Nevessignsky, Michel Toungouz; Vangenot, Christelle; van Walraven, Anne-Marie; Vidan-Jeras, Blanka; Viken, Marte K & Nunes, José Manuel de Abreu (2013). HLA-NET: A REAL EXAMPLE OF 'NETWORKING IN IMMUNOGENETICS'. Tissue Antigens.  ISSN 0001-2815.  81(5), s 300- 301
• Tinholt, Mari; Viken, MK; Borresen-Dale, AL; Kristensen, V; Karesen, R; Schlichting, E; Oystein, G; Lie, Benedicte Alexandra; Dahm, Anders Erik A; Skretting, Grethe; Sandset, Per Morten & Iversen, Nina (2013). The link between the hemostatic system and cancer: A genotype-phenotype study in breast cancer patients. Thrombosis Research.  ISSN 0049-3848.  131, s S75- S76
• Berge, Tone; Leikfoss, Ingvild Sørum; Spurkland, Anne; Lie, Benedicte Alexandra & Harbo, Hanne Flinstad (2012). Multiple sclerosis-associated single nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in thymic tissue.
• Chen-Xu, Michael; Topless, Ruth; McKinney, Cushla; Merriman, Marilyn E.; Phipps-Green, Amanda; Dalbeth, Nicola; Gow, Peter J.; Harrison, Andrew A.; Highton, John; Jones, Peter B; Nissen, Michael; Smith, Malcolm D.; van Rij, André; Jones, Greg T.; Rodríguez-Rodríguez, Luis; Fernandez-Gutierrez, Benjamin; Teruel, Maria; Balsa, Alejandro; Pascual-Salcedo, Dora; Ortiz, Ana M.; Gonzalez-Gay, Miguel A.; Steer, Sophia; Mæhlen, Marthe Thoresen; Lie, Benedicte Alexandra; Wordsworth, B. Paul; Stamp, Lisa K.; Martin, Javier & Merriman, Tony R. (2012). Replication of association of the interleukin 23 receptor rs1343151 variant with rheumatoid arthritis in Caucasian sample sets. Annals of the Rheumatic Diseases.  ISSN 0003-4967.  71(1), s 155- U1 . doi: 10.1136/annrheumdis-2011-200591
• Leikfoss, Ingvild S; Mero, Inger-Lise; Dahle, Maria Krudtaa; Lie, Benedicte Alexandra; Harbo, Hanne Flinstad; Spurkland, Anne & Berge, Tone (2012). Multiple Sclerosis Associated Single Nucleotide Polymorphisms in CLEC16A Correlate with Reduced SOCS1 and DEXI Expression in Thymic Samples. Scandinavian Journal of Immunology.  ISSN 0300-9475.  76(2), s 196- 196
• Merriman, Tony R.; Dalbeth, Nicola; Harrison, Andrew; Highton, John; Stamp, Lisa K.; Smith, Malcolm D.; Lie, Benedicte Alexandra; Kvien, Tore Kristian; Radstake, Timothy R.D.J.; Coenen, Marieke J.H.; Franke, Barbara; Broen, Jasper; van Riel, Piet; Barrera, Pilar; Steer, Sophia; Merriman, Marilyn E.; Phipps-Green, Amanda; Topless, Ruth; Zamanpoor, Mansour & Tain, WRW (2012). The Sex-Determining Region Y Box 6 Locus: Shared Genetic Susceptibility Between Rheumatoid Arthritis and Psychotic Disorder. Arthritis and Rheumatism.  ISSN 0004-3591.  64(10), s S505- S506
• Naess, Sigrid; Anmarkrud, Jarl Andreas; Björnsson, Einar; Al Mamari, Said; Juran, Brian D.; Lazaridis, Konstantios N; Chapman, Roger W.; Bergquist, Annika; Schrumpf, Erik; Lie, Benedicte Alexandra; Boberg, Kirsten Muri; Karlsen, Tom Hemming & Hov, Johannes Espolin Roksund (2012). HLA associations in small-duct compared with large-duct primary sclerosing cholangitis. Hepatology.  ISSN 0270-9139.  56, s 1134A- 1134A
• Tautz, Lutz; Vang, Torkel; Liu, Wallace; Delacroix, Laurence; Wu, Shuangding; Vasile, Stefan; Dahl, Russell; Yang, Li; Musumeci, Lucia; Francis, Dana; Landskron, Johannes; Tasken, Kjetil; Tremblay, Michel L.; Lie, Benedicte Alexandra; Page, Rebecca; Mustelin, Tomas; Rahmouni, Souad & Rickert, Robert C. (2012). Dynamic interaction between lymphoid tyrosine phosphatase and C-terminal Src kinase controls T cell activation. The FASEB Journal.  ISSN 0892-6638.  26
• Tengesdal, Guro; Lie, Benedicte Alexandra; Boberg, Kirsten Muri; Karlsen, Tom Hemming & Hov, Johannes Espolin Roksund (2012). Survey of nongenetic risk factors suggests that tobacco exposure, coffee consumption, the use of oral contraception and the number of pregnancies could affect disease risk or presentation of primary sclerosing cholangitis. Hepatology.  ISSN 0270-9139.  56, s 301A- 301A
• Viken, Marte K; Flåm, Siri Tennebø; Sollid, Ludvig Magne; Skrivarhaug, Torild; Dahl-Jørgensen, Knut & Lie, Benedicte Alexandra (2012). STUDY OF THE HLA-DRB1 AND-DQB1 GENES IN PATIENTS WITH COEXISTING TYPE 1 DIABETES AND CELIAC DISEASE. Tissue Antigens.  ISSN 0001-2815.  79(6), s 584- 584
• Zaiss, Dietmar; Bekker, Cornelis; Grne, Andrea; Lie, Benedicte Alexandra & Sijts, Alice (2012). Proteasome immunosubunits protect against the development of CD8 T-cell-mediated autoimmune diseases. Molecular Immunology.  ISSN 0161-5890.  51(1), s 30- 31 . doi: 10.1016/j.molimm.2012.02.084
• Eike, Morten Christoph; Skinningsrud, Beate; Lie, Benedicte Alexandra; Husebye, Eystein Sverre & Undlien, Dag Erik (2011). No association with RFX, CCR5 or CD226 polymorphisms in Norwegian Addison’s disease patients. Vis sammendrag

  Autoimmune Addison’s disease (AAD) is a rare disease characterised by autoimmune destruction of the adrenal cortex. As AAD patients frequently suffer from concomitant autoimmune diseases of other organs, AAD is an interesting model disease for susceptibility factors common to autoimmunity. Accordingly, many of the genes involved in other autoimmune diseases have also been associated with AAD. In this study, we investigated two candidate polymorphisms strongly associated with other autoimmune diseases, a 32 bp deletion (Δ32) in the chemokine C-C motif receptor 5 gene (CCR5) and the rs763361 C>T Gly307Ser SNP in the CD226 gene. In addition, SNPs in the class II MHC transactivator (CIITA) gene has previously been associated with disease in our AAD patients and a number of other autoimmune diseases. We therefore investigated the possibility for presence of susceptibility factors in the genes of the three coregulatory factors of CIITA, the regulatory factor X genes (RFXANK, RFX5 and RFXAP), with a total of eight tagging SNPs. 416 patients with Addison’s disease (321 for rs763361) and 1029 healthy blood donors were genotyped, all of Norwegian origin. A priori, we had ≥80% power to detect an OR above 1.41-1.85 or below 0.70-0.45, depending on minor allele frequency. Two of the tagging SNPs, in RFX5 and RFXAP respectively, were not in Hardy-Weinberg equilibrium in the control population (p<0.05), and were therefore excluded. No significant associations were found between Addison’s disease and either polymorphism, nor with haplotypes of any of the RFX SNPs (p>0.05). However, a tendency for a protective effect was observed for patients homozygous for CCR5Δ32 (recessive OR 0.39, 95% CI 0.11 to 1.31, p=0.11), similar to what has been reported earlier for patients with type 1 diabetes. In conclusion, no significant disease association was found in this study, possibly due to limited power. However, a tendency was observed for the 32 bp deletion polymorphism in the CCR5 gene, which could merit follow-up studies in other AAD cohorts.

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