The significant association of Taq1A genotypes in DRD2/ANKK1 with smoking cessation in a large-scale meta-analysis of Caucasian populations

摘要

Although a number of studies have analyzed the relation between the DRD2/ANKK1 gene Taq1A polymorphism and smoking cessation, the results remain controversial. The primary objective of the present study was to determine whether this variant indeed has any effect on smoking cessation. The A1-dominant model that considers A1/* (*=A1 or A2) and A2/A2 as two genotypes and compares their frequencies in current and former smokers was applied. A total of 22 studies with 11 075 subjects were included in the meta-analyses. Considering the potential influence of between-study heterogeneity, we conducted stratified meta-analyses with the Comprehensive Meta-Analysis statistical software (version 2.0). Results based on either cross-sectional or longitudinal studies consistently showed a statistically significant association between Taq1A A1/* genotypes and smoking cessation. Further, a more significant association of the variant with smoking cessation was detected when both types of studies were combined. However, there was marginal evidence of heterogeneity among studies (I²=33.9% P=0.06). By excluding other ethnicities and subjects with cancer, the meta-analysis on the basis of 9487 Caucasians demonstrated that Taq1A A1/* genotypes indeed were significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.22; 95% CI 1.11–1.34; P=3.9 × 10⁻⁵ for both models). No evidence of between-study heterogeneity or publication bias was observed. Thus, we conclude that the polymorphism of Taq1A has an important role in the process of abstaining from smoking, and smokers carrying A2/A2 genotype have a higher likelihood of smoking cessation than those who carry A1/A1 or A1/A2.