Association between CTLA-4 exon-1 +49A/G polymorphism and asthma: an updated meta-analysis

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to asthma are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and asthma, a meta-analysis of 15 published case-control studies was performed. 15 studies meeting our inclusion criteria comprising 4006 asthma cases and 3729 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 asthma cases and control on the basis of all studies, GG + GA versus AA (OR = 0.76, 95% CI: 0.62-0.93; P = 0.008). When stratifying for the race, the phenomenon was found that asthma cases had a significantly higher frequency of GG/GA versus AA (OR = 0.71; 95% CI: 0.51-0.99; P = 0.04) than control in Caucasian. Stratifying subjects by age indicated an association between CTLA-4 +49 GG + GA genotype and asthma in children (OR = 0.75; 95% CI: 0.62-0.90; P = 0.002), but no association in adults (OR = 0.93; 95% CI: 0.76-1.14; P = 0.48). Furthermore, significant association was observed in atopic asthma under the fixed-effects model (GG + GA vs. AA: P = 0.03, OR = 0.81, 95% CI = 0.67-0.98, P heterogeneity = 0.22). Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for asthma susceptibility, at least in Caucasian, children, and patients with atopy status.