Li Hua, Hu Yonghe, Zhang Tao, Liu Yang, Wang Yantang, Yang Tai, Li Minhui, Luo Qiaoli, Cheng Yu, Zou Qiang
Department of Oncology, Chengdu Military General Hospital, Chengdu 610083, China.
Clin Dev Immunol. 2013;2013:891306. doi: 10.1155/2013/891306. Epub 2013 Sep 3.
Previous genome-wide association study by WTCCC identified many susceptibility loci of common autoimmune diseases in British, including rheumatoid arthritis (RA). Because of the genetic heterogeneity of RA, it is necessary to replicate these susceptibility loci in other populations. Here, three SNPs with strong RA association signal in the British were analyzed in Han Chinese, and two SNPs (rs6457617 and rs11761231) were genotyped in the test cohort firstly. The rs6457617 was significantly associated with RA in the test cohort. The individuals bearing the homozygous genotype CC had 0.39-fold risk than these bearing the wild-type genotype TT (P = 0.004, OR 0.39, [95% CI 0.21-0.74]). And the protective effect of allele C was confirmed in another validation cohort with 1514 samples (P genotye CC/TT = 5.9 × 10(-10), OR 0.34, [95% CI 0.24-0.48]). The rs6457617 can be used as a tagSNP of HLA-DQA1∗03 which encoded MHC-II α chain. Since MHC restriction is important for primary T-cells in positive selection and negative selection stages, MHC protein polymorphisms may be implicated in shaping the T-cell repertoire, including the emergence of a T-cell clone involved in the inflammatory arthritis.
韦尔科姆基金会病例对照关联研究(WTCCC)之前开展的全基因组关联研究在英国人群中确定了许多常见自身免疫性疾病的易感基因座,包括类风湿关节炎(RA)。由于RA存在遗传异质性,有必要在其他人群中对这些易感基因座进行重复验证。在此,我们对英国人群中具有强烈RA关联信号的3个单核苷酸多态性(SNP)在汉族人群中进行了分析,并首先在测试队列中对2个SNP(rs6457617和rs11761231)进行了基因分型。rs6457617在测试队列中与RA显著相关。携带纯合基因型CC的个体比携带野生型基因型TT的个体风险低0.39倍(P = 0.004,比值比0.39,[95%置信区间0.21 - 0.74])。并且在另一个包含1514个样本的验证队列中证实了等位基因C的保护作用(P基因型CC/TT = 5.9×10⁻¹⁰,比值比0.34,[95%置信区间0.24 - 0.48])。rs6457617可作为编码MHC - IIα链的HLA - DQA1∗03的标签SNP。由于MHC限制在初始T细胞的阳性选择和阴性选择阶段很重要,MHC蛋白多态性可能参与塑造T细胞库,包括参与炎性关节炎的T细胞克隆的出现。