Abstract
BackgroundAlthough some effects of gene–gene interactions on nicotine–dopamine metabolism for smoking behavior have been reported, polymorphisms of cytochrome P450 (CYP) 2A6 and catechol-O-methyltransferase (COMT) have not been studied together to determine their effects on smokers. The aim of this study was to investigate the effects of the interaction between the CYP 2A6 and COMT genes on smoking behavior in young Taiwanese men.ResultsA self-report questionnaire regarding smoking status was administered to 500 young men. Polymorphisms of the CYP 2A6 and COMT genes as well as urinary nicotine and urinary cotinine levels were determined. The odds ratio for starting smoking was significantly lower in subjects carrying a CYP2A6 low activity/variant COMT rs4680 genotype than in those possessing a CYP2A6 wild-type/variant COMT rs4680 genotype (0.44, 95% confidence interval = 0.19–0.98, P = 0.043). Comparisons of Fagerstrom Test for Nicotine Dependence (FTND), Physiological Cigarette Dependence Scale (PCDS), and Cigarette Withdrawal symptoms (CWS-21) among the smokers with different CYP2A6/COMT polymorphisms were not significantly different. The adjusted urinary nicotine concentrations were not significantly different between the two groups carrying different genotypes. The adjusted urinary cotinine level was significantly different between the COMT rs4680 wild-type group and COMT rs4680 variant group [92.46 ng/μL vs. 118.24 ng/μL (median value), P = 0.041] and between the COMT rs4680 wild-type/COMT rs165599 variant group and COMT rs4680 variant/COMT rs165599 variant group (97.10 ng/μL vs. 122.18 ng/μL, P = 0.022).ConclusionsThese findings suggest that a single nucleotide polymorphism (rs4680) of the COMT gene and the interaction between the CYP 2A6 and COMT genes affect smoking status in young Taiwanese men.
Highlights
Some effects of gene–gene interactions on nicotine–dopamine metabolism for smok‐ ing behavior have been reported, polymorphisms of cytochrome P450 (CYP) 2A6 and catechol-O-methyltransferase (COMT) have not been studied together to determine their effects on smokers
We evaluated the effect of the interactions between different gene combinations on smoking status (Table 2), smoking intensity (Additional file 2: Table S2), nicotine dependence (FTND), physiological cigarette dependence (PCDS), nicotine toxicity and withdrawal symptoms (CWS-21) (Additional file 3: Table S3), and urine nicotine/cotinine concentration (Table 3) in young men
Using the frequencies of cytochrome P450 2A6 (CYP2A6)*1A/*1A, CYP2A6*1A/*1B, and CYP2A6*1B/*1B as examples, the distributions of CYP2A6 genotypes agreed with Hardy–Weinberg equilibrium: P = 0.713 and 0.332 for current smokers and never smokers, respectively
Summary
Some effects of gene–gene interactions on nicotine–dopamine metabolism for smok‐ ing behavior have been reported, polymorphisms of cytochrome P450 (CYP) 2A6 and catechol-O-methyltransferase (COMT) have not been studied together to determine their effects on smokers. Nicotine is the major psychoactive ingredient in tobacco, and it modulates dopamine activity in the midbrain, which contributes to the development and maintenance of rewarding behaviors such as smoking [4]. Smokers modulate their smoking to maintain brain nicotine levels within a certain concentration range, and factors that alter nicotine clearance affect smoking behavior [4]. We hypothesized that, for Taiwanese individuals, polymorphisms in the CYP2A6 gene that affect smoking status could be different from those in other ethnic groups
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