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CTLA-4 +49 G/A Polymorphism Confers Autoimmune Disease Risk: An Updated Meta-Analysis
Ke Wang1, Qin Zhu1, Yunjie Lu1
1Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
Background:
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.
Materials And Methods:
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.
Results:
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.
Conclusion:
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.