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

Abstract

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.

Meta-Analysis Reveals Significant Association of the 3′-UTR VNTR inSLC6A3with Alcohol Dependence

“…Finally, because of the insufficient number of studies on other variants, we could not examine the gene-by-gene or SNP-by-SNP interaction, which contribute significantly to vulnerability for complex addictive phenotypes. For example, the polymorphism of Taq 1A of DRD2 has been suggested to interact with the polymorphism of VNTR of SLC6A3 , both of which may have a role in smoking cessation (Ma et al, 2015b, Ma et al, 2015a). To date, multiple lines of evidence (Wang et al, 2013) have shown that DRD2 Taq 1A polymorphism is significantly associated with AD, suggesting an interactive function of these two variants for AD as well.…”

“…Particularly, the dopaminergic mesocorticolimbic reward pathways have been linked to the pathogenesis of addictions, including alcoholism. Consequently, genes with a dopaminergic function have received much attention in relation to the etiology of AD and other addictions (Muramatsu and Higuchi, 1995, van der Zwaluw et al, 2009, Ma et al, 2014, Ma et al, 2015a). …”

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis

“…On a psychiatric level, this DRD2Taq1A polymorphism is associated with depression and addiction behaviors (15). This genotype is involved not only in the process of development of addiction, but also in treatment response; in particular, DRD2*A1 has an important role in the process of abstinence from smoking (16), it can predict a good response when disulfiram is used for the treatment of cocaine addiction (17) and it has also been related with a higher probability of fatal methamphetamine intoxication (18). DRD2 A1/A1 genotype appears associated with the development of an antisocial personality disorder (19) as well and with psychopathic-like behaviors in alcoholdependent patients (20).…”

Meta-analytic method reveal a significant association of theBDNF Val66Met variant with smoking persistence based on a large samples

“…As documented in previous studies [15,18,44], we defined the elements of smoking behaviors as comparing the status of smoking: (1) use ever smoking versus (vs.) never smoking to assess initiation of smoking, (2) use current smoking vs. never smoking to assess maintaining smoking (i.e., smoking persistence), and (3) use current smoking vs. ex-smoking to assess smoking cessation. In the accepted studies, the data for smoking was mainly concentrated on smoking persistence.…”

“…Thus, a large and growing interests in exploring the risk of genetic components for smoking and subsequent nicotine dependence. Many studies based on candidate genes and several large genome-wide association studies (GWAS) have reported a great number of variants relevant to smoking behaviors [14][15][16][17][18][19]. One of the most promising results in GWASs is genetic variants mapped in the CHRNA5-A3-B4 gene cluster on the chromosome of 15q24-25.1 region are remarkably linked with nicotine dependence [16,19].…”