Role of CD226 Rs763361 Polymorphism in Susceptibility to Multiple Autoimmune Diseases

Background: Gly307Ser (rs763361) polymorphism in Cluster of Differentiation 226 (CD226) gene has been implicated in susceptibility to autoimmune diseases (ADs) with controversial results. This study aimed to conduct a meta-analysis for examining the relationship between CD226 rs763361 polymorphism and ADs risk. Methods: a literature search was performed to identify relevant studies published in Embase, PubMed, Wanfang, and China National Knowledge Infrastructure. In the most appropriate genetic models, pooled odds ratio (OR) with 95% confidence interval (CI) was calculated for evaluating the strength of the associations. Besides standard meta-analysis, cumulative meta-analysis was also conducted to assess the trend in OR over time. Also, we performed subgroup and sensitivity analysis, and checked for the heterogeneity and publication bias. Results: Twenty-nine reports with 51 independent studies, comprising 18157 cases and 29904 controls, were enrolled in this meta-analysis. Among overall and various ethnic populations (Europeans, Asians, Africans, and South Americans), CD226 rs763361 polymorphism was significantly associated with ADs susceptibility; in the subgroup analysis by disease type, rs763361 polymorphism revealed significant associations with the risk of RA, SLE, T1D, and MS. The sensitivity analysis and cumulative meta-analysis confirmed the stability and robustness of these significant results. However, no evidence of stable significant association emerged in the subgroup analysis of SSc. Conclusion: These findings demonstrate that CD226 rs763361 polymorphism confers susceptibility to ADs in the overall population, Europeans, Asians, Africans, and South Americans. rs763361 polymorphism in CD226 gene may be a potential susceptible predictor of ADs especially RA, SLE, T1D, and MS.