Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease
Elaine F. Remmers,Fulya Cosan,Yohei Kirino,Michael J. Ombrello,Neslihan Abaci,Colleen Satorius,Julie M. Le,Barbara Yang,Benjamin D. Korman,Aris Cakiris,Oznur Aglar,Zeliha Emrence,Hulya Azakli,Duran Ustek,Ilknur Tugal-Tutkun,Gulsen Akman-Demir,Wei-Wei Chen,Christopher I. Amos,Michael B. Dizon,Afet Akdag Kose,Gülsevim Azizlerli,Burak Erer,Oliver J. Brand,Virginia G. Kaklamani,Phaedon G. Kaklamanis,Eldad Ben-Chetrit,Miles Stanford,Farida Fortune,Marwen Ghabra,William E R Ollier,Young-Hun Cho,Dongsik Bang,John M O'Shea,Graham R. Wallace,Massimo Gadina,Daniel L. Kastner,Ahmet Gül +36 more
TLDR
The known association of Behçet's disease with HLA-B*51 was confirmed and a second, independent association within the MHC Class I region was identified and the disease-associated IL10 variant was associated with diminished mRNA expression and low protein production.Abstract:
Behcet'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 Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet'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 x 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 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 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.read more
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