Objective: The aim of this study was to explore whether the CD226 rs763361 polymorphism confers susceptibility to autoimmune diseases.
Methods: A meta-analysis was conducted on the associations between the CD226 rs763361 polymorphism and autoimmune diseases using: 1) allele contrast, and 2) the recessive, 3) dominant and 4) additive models.
Results: Ten articles that included 17 comparative studies on a total of 8900 patients and 10,295 controls were included in the meta-analysis. These studies were performed on seven European, five Asian and five South American sample populations. Meta-analysis of all study subjects revealed an association between the CD226 rs763361 T allele and the susceptibility to autoimmune diseases (odds ratio; OR 1.162, 95% confidence interval; CI 1.097-1.230, p < 1.0 × 10(-8)). Stratification by ethnicity indicated an association between the CD226 rs763361 T allele and autoimmune disease in Europeans and South Americans (OR 1.134, 95% CI 1.079-1.191, p = 6.7 × 10(-7); OR 1.308, 95% CI 1.160-1.475, p = 1.1 × 10(-5)) and between the CD226 rs763361 TT genotype and autoimmune disease in Asians (OR 1.366, 95% CI 1.130-1.650, p = 0.001). Disease-specific meta-analysis showed an association between systemic lupus erythematosus (SLE) and the CD226 rs763361 T allele (OR 1.150, 95% CI 1.040-1.271, p = 0.006), but no association between rheumatoid arthritis and the CD226 rs763361 polymorphism (OR for the T allele 1.207, 95% CI 0.913-1.596, p = 0.187). On the other hand, associations were found between the CD226 rs763361 T allele and systemic sclerosis (SSc) and type 1 diabetes (T1D) (OR 1.126, 95% CI 1.020-1.244, p = 0.019; OR 1.353, 95% CI 1.102-1.660, p = 0.004).
Conclusions: This meta-analysis demonstrates the CD226 rs763361 polymorphism confers susceptibility to autoimmune disease in Europeans, South Americans and Asians, and in particular, shows that the CD226 rs763361 polymorphism is associated with SLE, SSc and T1D. These results support the existence of an association between the CD226 gene and a subgroup of autoimmune diseases.