Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to systemic lupus erythematosus are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and SLE, a meta-analysis of 18 published case–control studies was performed. 18 studies meeting our inclusion criteria comprising 1806 SLE cases and 2,490 controls were included. The effect summary odds ratio (OR) and 95 % confidence intervals were obtained. Publication bias was tested by funnel plot, Egger’s test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between SLE cases and control on the basis of all studies, GG versus AA (OR = 1.53, 95 % CI: 1.12–2.10), GG versus GA/AA (OR = 1.30, 95 % CI: 1.04–1.64), GG versus GA (OR = 1.27, 95 % CI: 1.03–1.55). When stratifying for the race, the phenomenon was found that SLE cases had a significantly higher frequency of GG/GA versus AA (OR = 1.58, 95 % CI: 1.23–2.03), GG versus AA (OR = 1.89, 95 % CI: 1.23–2.91), GG versus GA/AA(OR = 1.39, 95 % CI: 1.03–1.89), GA versus AA(OR = 1.38, 95 % CI: 1.06–1.80) and G versus A(OR = 1.34, 95 % CI: 1.07–1.67) than control in Asians. Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for SLE susceptibility, at least in Asians. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of CTLA-4 exon-1 +49A/G polymorphism with SLE susceptibility.