Updated analysis of studies on the cytotoxic T-lymphocyte-associated antigen-4 gene A49G polymorphism and Hashimoto's thyroiditis risk

Published data on the association between the cytotoxic T-lymphocyte-associated antigen-4 gene A49G polymorphism and the risk for Hashimoto's thyroiditis (HT) are inconclusive. A meta-analysis was performed to derive a more precise estimation. Published case-control studies in English or Chinese were identified. In total, 24 studies with 2295 cases and 4521 controls were investigated. A random-effect model was performed irrespective of between-study heterogeneity. Study quality was assessed in duplicate, and subgroup analyses were conducted by ethnicity or age. Overall, the 49G allele was associated with an increase in HT risk [odds ratio (OR) = 1.31; 95% confidence interval (95% CI) = 1.17-1.47; P < 0.00001]. In a subgroup analysis by ethnicity, comparison of allele 49G with 49A generated a 27% increased risk among East Asians (OR = 1.48; 95% CI = 1.24-1.76; P < 0.00001) and whites (OR = 1.27; 95% CI = 1.12-1.44; P = 0.0002). We also found an increased risk among adults (OR = 1.31; 95% CI = 1.17-1.47; P < 0.00001) but not among children (OR = 1.44; 95% CI = 0.75-2.79; P = 0.27), possibly owing to the small sample sizes in children. No publication biases were observed. This meta-analysis suggested that the cytotoxic T-lymphocyte-associated antigen-4 gene 49G allele was associated with an increased HT risk, especially in adults.