Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a pivotal role in immune homeostasis. Dysregulated expression of CTLA-4 leads to many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes (T1D). There has been a controversial association between the CTLA-4 +49 G/A SNP (rs231775) and autoimmune diseases. Therefore, this meta-analysis was performed to assess the link between rs231775 and autoimmune disease risk.
We retrieved the available studies from PUBMED and EMBASE through February, 2016 and then performed meta-analyses that included all populations, as well as by ethnicity.
After evaluating data from 4732 patients and 6270 healthy controls that included both Caucasian and Asian ethnicities, we found that rs231775 is strongly associated with autoimmune disease incidence in a homozygote comparison (GG vs. AA, 95% confidence interval [95% CI] 1.382-2.401), in a heterozygote comparison (AG vs. AA, 95% CI 1.151-1.611), in an allelic model (T allele vs. G allele, 95% CI 1.109-1.441), in a dominant model (GG/AG vs. AA, 95% CI 1.220-1.787), and in a recessive model (GG vs. AA/AG, 95% CI 1.128-1.661). The OR (odds ratio) from all models suggested a very significant association between rs231775 and autoimmune diseases.
Our present study indicates that CTLA-4 +49 G/A (rs231775) is associated with the susceptibility of autoimmune disease. Hence, rs231775 might be utilized as a diagnostic biomarker in both Asian and Caucasian populations.