Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease


REMMERS E. F. , Cosan F., KIRINO Y., OMBRELLO M. J. , Abaci N. , SATORIUS C., ...Daha Fazla

NATURE GENETICS, cilt.42, ss.698-704, 2010 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 42 Konu: 8
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1038/ng.625
  • Dergi Adı: NATURE GENETICS
  • Sayfa Sayıları: ss.698-704

Özet

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.