4.5 Article

CIITA variation in the presence of HLA-DRB1*1501 increases risk for multiple sclerosis

期刊

HUMAN MOLECULAR GENETICS
卷 19, 期 11, 页码 2331-2340

出版社

OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddq101

关键词

-

资金

  1. NIH/NINDS [R01 NS049477]
  2. NMSS [RG4201-A-1, RG2901, RG4201]
  3. NIH/NIAID [F31 AI075609, U19 AI067152]
  4. Medical Research Council [G0700061]
  5. Cambridge NIHR Biomedical Research Centre
  6. Medical Research Council [G0700061, G0801418B] Funding Source: researchfish
  7. MRC [G0700061] Funding Source: UKRI

向作者/读者索取更多资源

The MHC class II transactivator gene (CIITA) is an important transcription factor regulating gene required for HLA class II MHC-restricted antigen presentation. Association with HLA class II variation, particularly HLA-DRB1*1501, has been well-established for multiple sclerosis (MS). In addition, the -168A/G CIITA promoter variant (rs3087456) has been reported to be associated with MS. Thus, a multi-stage investigation of variation within CIITA, DRB1*1501 and MS was undertaken in 6108 individuals. In stage 1, 24 SNPs within CIITA were genotyped in 1320 cases and 1363 controls (n = 2683). Rs4774 (missense +1614G/C; G500A) was associated with MS (P = 4.9 x 10(-3)), particularly in DRB1*1501 +individuals (P = 1 x 10(-4)). No association was observed for the -168A/G promoter variant. In stage 2, rs4774 was genotyped in 973 extended families; rs4774*C was also associated with increased risk for MS in DRB1*1501+ families (P = 2.3 x 10(-2)). In a third analysis, rs4774 was tested in cases and controls (stage 1) combined with one case per family (stage 2) for increased power. Rs4774*C was associated with MS (P = 1 x 10(-3)), particularly in DRB1*1501+ cases and controls (P = 1 x 10(-4)). Results obtained from logistic regression analysis showed evidence for interaction between rs4774*C and DRB1*1501 associated with risk for MS (ratio of ORs = 1.72, 95% CI 1.28-2.32, P = 3 x 10(-4)). Furthermore, rs4774*C was associated with DRB1*1501+ MS when conditioned on the presence (OR = 1.67, 95% CI = 1.19-2.37, P = 1.9 x 10(-3)) and absence (OR = 1.49, 95% CI = 1.15-1.95, P = 2.3 x 10(-3)) of CLEC16A rs6498169*G, a putative MS risk allele adjacent to CIITA. Our results provide strong evidence supporting a role for CIITA variation in MS risk, which appears to depend on the presence of DRB1*1501.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据