The association between CTLA-4 (+49 A/G) polymorphism and susceptibility to ankylosing spondylitis: a meta-analysis

The objective of the present meta-analysis was to investigate whether or not cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) polymorphisms are associated with ankylosing spondylitis (AS) susceptibility.

A systematic search was conducted from the PubMed, ENBASE, and Springer link database up to April 2014. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association between CTLA-4 (+49 A/G) and AS risk. A subgroup analysis based on geographic region and a sensitivity analysis were also conducted.

Five studies were eligible for meta-analysis, including 918 cases and 845 controls. The results showed that no significant association was found between AS and CTLA-4 (+49 A/G) for the additive model (G vs. A), dominant model (GG + AG vs. AA), co-dominant model (GG vs. AA, AG vs. AA) and recessive model (GG vs. AG + AA). The OR was 1.09 (95% CI, 0.87-1.38), 1.16 (95% CI, 0.89-1.51), 1.05 (95% CI, 0.75-1.46), 1.15 (95% CI, 0.86-1.52) and 0.99 (95% CI, 0.79-1.23), respectively. Although subgroup analysis demonstrated no association between CTLA-4 (+49 A/G) polymorphisms and susceptibility to AS in Europe and Taiwan, an association was found in Iran through both the co-dominant and dominant models. Exclusion of any individual study did not alter the significance of the final outcome, excepting the result by omitting the study by Huang et al.

The present results suggest that the CTLA-4 may not be a major susceptibility locus in humans with AS. The relationship between them may be affected by different geographic populations.