Abstract
Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10−8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10−18, odds ratio = 1.45, 95% CI 1.34–1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10−9, OR = 1.28, 95% CI 1.18–1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.
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Acknowledgements
This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the US National Institutes of Health, by the Istanbul University Research Fund and by the UK Behçet's Syndrome Society. This work was also supported in the part by US NIH grants to C.I.A. (AR44422 and PC30CA016772). We thank all of our subjects for their enthusiastic support of our studies aiming to understand and find better treatments for Behçet's disease, and we thank O. Aksakalli and H. Ustek for their help in blood collection.
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Study design: E.F.R., F.C., Y.K., M.J.O., B.D.K., D.U., W.C., C.I.A., J.O., M. Gadina, D.L.K., A.G. Analysis: E.F.R., Y.K., M.J.O., B.Y., W.C., C.I.A., M.B.D., G.R.W., M. Gadina, D.L.K., A.G. Sample procurement and data generation: E.F.R., F.C., Y.K., M.J.O., N.A., C.S., J.M.L., B.Y., B.D.K., A.C., O.A., Z.E., H.A., D.U., I.T.-T., G.A.-D., W.C., C.I.A., M.B.D., A.A.K., G.A., B.E., O.J.B., V.G.K., P.K., E.B.-C., M.S., F.F., M. Ghabra., W.E.R.O., Y.-H.C., D.B., J.O., G.R.W., M. Gadina, D.L.K., A.G. Writing: E.F.R., Y.K., M.J.O., B.Y., C.I.A., J.O., M. Gadina, D.L.K., A.G.
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Remmers, E., Cosan, F., Kirino, Y. et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nat Genet 42, 698–702 (2010). https://doi.org/10.1038/ng.625
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DOI: https://doi.org/10.1038/ng.625
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