Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease
Makaleler > Tam Makale · 2013
Yazarlar: Travis HUGHES, Patrick COIT, Adam ADLER, Vuslat Yilmaz, Kenan AKSU, Nursen Duzgun, Gökhan KESER, AYŞE ÇEFLE, AYTEN YAZICI, Andac ERGEN, Erkan Alpsoy, Carlo SALVARANI, Bruno CASALI, Ina KOETTER, Javier GUTIERREZ-ACHURY, Cisca WIJMENGA, Suzan GÜVEN, Guher Saruhan-Direskeneli, Amr H. SAWALHA
Nature Genetics, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2013, cilt 45, ss 319-324
DOI: 10.1038/ng.2551
Özet
Behcet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behcet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behcet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behcet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 x 10(-5)). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 x 10(-26)), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 x 10(-14)) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 x 10(-18)) were also identified and replicated.