Meta-analysis reveals significant association of 3′-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations

Many studies have examined the association between SLC6A3 3′-UTR VNTR polymorphism and smoking cessation; however, the results are inconclusive, primarily because of the small to moderate-size samples. The primary goal of this study was to determine whether this polymorphism has any effect on smoking cessation by a meta-analysis of all reported studies. We adopted a 9-repeat dominant model that considers 9-repeat and non 9-repeat as two genotypes and compared their frequencies in former vs. current smokers. Eleven studies with 5,480 participants were included. Considering the presence of study heterogeneity and differences in the availability of information from each study, three separate meta-analyses were performed with the Comprehensive Meta-Analysis statistical software (v. 2.0). The first meta-analysis provided evidence of association between the 9-repeat genotype and smoking cessation under the fixed-effects model (pooled odds ratio [OR] 1.13; 95% confidence interval [CI] 1.01, 1.27; P = 0.037) but not in the random-effects model (pooled OR 1.11; 95% CI 0.96, 1.29; P = 0.159). Given the marginal evidence of heterogeneity among studies (P = 0.10; I2 = 35.9%), which likely was caused by inclusion of an Asian-population treatment study with an opposite effect of the polymorphism on smoking cessation, we excluded these data, revealing a significant association between the 9-repeat genotype and smoking cessation under both the fixed- and random-effects models (pooled OR 1.15; 95% CI 1.02, 1.29; P = 0.02 for both models). By analyzing adjusted and unadjusted results, we performed the third meta-analysis, which showed consistently that the 9-repeat genotype was significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.17; 95% CI 1.04, 1.31; P = 0.009 for both models). We conclude that the 3′-UTR VNTR polymorphism is significantly associated with smoking cessation, and smokers with one or more 9-repeat alleles have a 17% higher probability of smoking cessation than smokers carrying no such allele.