Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers.
ABSTRACT Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, which is important in mediating drug reward such as nicotine in tobacco smoke. Different COMT alleles encode enzyme whose activity varies from three- to fourfold that may affect dopamine levels and alter subjective effects of nicotine. Recent evidence also suggests that a COMT polymorphism may be especially important in determining an individual's predisposition to developing nicotine dependence.
We studied the COMT Val108Met polymorphism in a male population of 203 current smokers, 66 former smokers, and 102 non-smokers. The age-adjusted odds ratios were estimated by multiple logistic regression models.
The results showed no significant association of the COMT Val108Met with initiation, persistent smoking, or smoking cessation. However, current smokers with the Met allele had significantly higher Fagerstrom Test for Nicotine Dependence scores (7.5 +/- 2.1 vs 6.8 +/- 1.8, p = 0.018) and started smoking significantly earlier (18.4 +/- 4.9 vs 20.1 +/- 5.9 years, p = 0.036).
These results suggest that the COMT Val108Met polymorphism may not influence smoking status in a Chinese male population but may influence the age at which smoking started and smoking severity among smokers. However, the findings must be regarded as preliminary because of the relatively small sample size and marginal associations and should be replicated in a larger cohort.
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ABSTRACT: The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight abstinent smokers received saline followed by 0.5 and 1.0 mg per 70 kg doses of nicotine, administered 30 min apart. Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking. Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes. The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure. These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers.The Pharmacogenomics Journal advance online publication, 5 March 2013; doi:10.1038/tpj.2013.1.The Pharmacogenomics Journal 03/2013; · 5.13 Impact Factor
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ABSTRACT: BACKGROUND: The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. METHODS: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior. RESULTS: We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence. CONCLUSIONS: Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.Nicotine & Tobacco Research 01/2013; · 2.48 Impact Factor
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ABSTRACT: The nicotine in cigarette smoke can stimulate the dopaminergic reward pathways. The catechol O-methyltransferase gene (COMT) and dopamine receptor 2 gene (DRD2) are dopamine-related genes. Genetic polymorphisms in these two genes are potential candidates in determining an individual's predisposition to cigarette smoking. The purposes of this study were to examine the association between two polymorphisms in COMT Val (108/158) Met and DRD2 Taq1B and anthropometric-biochemical parameters and to ascertain the association between these polymorphisms and cigarette smoking. The levels of anthropometric-biochemical parameters were determined. COMT Val (108/158) Met and DRD2 Taq1B polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. With regard to COMT Val (108/158) Met and DRD2 Taq1B polymorphisms, no differences were found in anthropometric-biochemical variables, except for thiocyanate concentration. Smoking status was significantly associated with COMT Val (108/158) Met polymorphism, but not associated with DRD2 Taq1B polymorphism. Logistic regression analysis showed that COMT Val (108/158) Met gene polymorphism, educational status, parental smoking, and alcohol consumption had statistically significant impacts on cigarette smoking. The results suggest that COMT Val (108/158) Met genetic polymorphisms, but not DRD2 Taq1B, may influence susceptibility to cigarette smoking among Thai males.Journal of Molecular Neuroscience 06/2012; · 2.89 Impact Factor