Significantly association of diabetes mellitus with CTLA-4 gene polymorphisms based on a meta-analysis of epidemiological evidence in Asians and non-Asians

We evaluated association of polymorphisms in the CTLA-4 gene with the risk of type 1 diabetes mellitus. Comprehensive meta-analysis was applied to case-control studies of the association between CTLA-4 and type 1 diabetes mellitus to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. We searched PubMed, Medline, Embase, Cochrane Library, and reference lists of relevant studies to February 2012, and made email contact with authors. For the case-control studies, we found 1) support for an association between CTLA-4 and type 1 diabetes mellitus, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. In all, although the association between CTLA-4 polymorphisms and type 1 diabetes mellitus is weak, we suggest that it is real. Further studies are needed to clarify what variant of CTLA-4 (or some related gene) accounts for this association.