Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
Nat Genet. 2013 Mar;45(3):319-24. doi: 10.1038/ng.2551. Epub 2013 Feb 10.
Behçet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B51 and Behçet'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 Behçet'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-B51 association in Behçet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10(-50)). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10(-26)), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10(-14)) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10(-18)) were also identified and replicated.
白塞病是一种炎症性疾病，其特征为反复发作的口腔和生殖器溃疡以及重要器官受累。定位 HLA-B51 与白塞病之间的遗传关联，并在人类白细胞抗原（HLA）区域中探索其他易感基因座，这一过程受到该区域强连锁不平衡的影响。我们对扩展 HLA 基因座中的 8572 个变体进行了基因分型，并对来自 2 个祖裔群体的 2 个独立白塞病队列中的 24834 个变体进行了推断和荟萃分析。基因分型的 SNP 用于推断 HLA-A、HLA-B、HLA-C、HLA-DQA1、HLA-DQB1 和 HLA-DRB1 基因座中的经典 HLA 等位基因。我们的数据表明，白塞病中强的 HLA-B51 关联是由位于 HLA-B 和 MIC-A 基因之间的变体（rs116799036：比值比（OR）=3.88，P=9.42×10(-50)）解释的。在 PSORS1C1 内还发现了另外 3 个独立的遗传关联（rs12525170：OR=3.01，P=3.01×10(-26)）、HLA-F-AS1 上游（rs114854070：OR=1.95，P=7.84×10(-14)）和 HLA-Cw*1602（OR=5.38，P=6.07×10(-18)），并进行了复制。
