Association of the CTLA-4 1722TC polymorphism and systemic lupus erythematosus: a systematic review and meta analysis

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important negative regulator of Tcell responses. The -1722TC polymorphism of the CTLA-4 gene may be associated with systemic lupus erythematosus (SLE) risk, but related results from previous studies have been inconsistent. We carried out a metaanalysis to assess this association more precisely. Methods: A systematic search through PubMed, Science Direct, and OVID, Iran doc, Iranmedex and SID (Scientific Information Database) databases was performed with the last search updated on December 30, 2011. The odds of ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. We evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The analyses were conducted using STATA software, version 11.0. Results: A total of 9 independent studies on the CTLA-4 gene -1722TC polymorphism and SLE, including 1422 cases and 1417 controls were used in this meta-analysis. In the present meta-analysis, we found a significant association between -1722TC polymorphism and SLE risk in the overall analysis (TT versus TC/CC: OR=1.18, 95%CI 0.84-1.66, p= 0.32; TT/TC versus CC: OR = 2.06, 95%CI 1.07–3.99, p= 0.03; TT versus CC: OR = 2.32, 95%CI 1.62–3.32, p< 0.001; TC versus CC: OR = 1.99, 95%CI 1.42–2.78, p<0.001; TT versus TC: OR = 1.2, 95%CI 0.86–1.66,p= 0.28; T versus C: OR = 1.22, 95%CI 0.91–1.64,p= 0.16). In the subgroup analysis by ethnicity, -1722TC polymorphism was significantly associated with SLE risk in Asian population. Conclusion: This meta-analysis suggests a significant association between -1722TC polymorphism and SLE susceptibility. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.