Guo S, Chen DF, Zhou DF, Sun HQ, Wu GY, Haile CN et al. Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers. Psychopharmacology 190: 449-456
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.
"In non-smokers, oscillatory changes due to acute nicotine administration are limited primarily to í µí»¼ rhythms, with increases observed in both PAF (Foulds et al. 1994; Harkrider et al. 2001) and frontal upper frequency í µí»¼ 2 power (Fisher et al. 2012a) during resting states, and increases in anterior í µí»¼ 2 during working memory tasks (Fisher et al. 2012b, 2013). Nicotine-induced oscillatory response differences between smokers and non-smokers may reflect genetic factors, including COMT (Beuten et al. 2006; Colilla et al. 2005; Guo et al. 2007), involved in smoking initiation and progression to dependence (Kendler et al. 1999; Maes et al. 2004) or individual differences in EEG. Little is known about the genetics underlying EEG traits or pharmacologically modulated EEG, but twin studies show that heritability of resting EEG oscillations is substantial (Stassen et al. 1987), particularly for PAF (Posthuma et al. 2001; Smit et al. 2005, 2006) and í µí»¼-band oscillations with 80–90% heritability estimates (Van Beijsterveldt & van Baal 2002; Van Beijsterveldt et al. 1996). "
[Show abstract][Hide abstract] ABSTRACT: Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol-O-methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting state electroencephalographic (EEG) oscillations. In a sample of 62 healthy nonsmoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double-blind, placebo controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in fronto-central regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT.
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"There was no gender difference in the genotype distribution. The allele frequencies in the present study are comparable to other studies with Chinese participants666768. Because of the limited number of subjects in the Met/Met group, we grouped the Val/Met and Met/Met subjects into the Met-carrier group in all subsequent analysis. "
[Show abstract][Hide abstract] ABSTRACT: Both genetic and environmental factors have been shown to influence decision making, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-environment interactions on decision making in a large healthy sample. Specifically, we examined how the frequently studied COMT Val(158)Met polymorphism interacted with an environmental risk factor (i.e., stressful life events) and a protective factor (i.e., parental warmth) to influence affective decision making as measured by the Iowa Gambling Task. We found that stressful life events acted as a risk factor for poor IGT performance (i.e., high reward sensitivity) among Met carriers, whereas parental warmth acted as a protective factor for good IGT performance (i.e., higher IGT score) among Val/Val homozygotes. These results shed some new light on gene-environment interactions in decision making, which could potentially help us understand the underlying etiology of several psychiatric disorders associated with decision making impairment.
"Third, given the risk of chance findings in genetic association studies and in an attempt to resolve the discrepancy between studies of the COMT rs4680 polymorphism and both heaviness of smoking (light vs. heavy smokers, as defined above) and persistent smoking (current smokers vs. ex-smokers), we combined our data with those from previous studies in community samples (Breitling et al., 2009; David et al., 2002; Guo et al., 2007; Omidvar et al., 2009; Shiels et al., 2008). We used our prepregnancy heaviness of smoking and first trimester persistent smoking data as described above. "
[Show abstract][Hide abstract] ABSTRACT: Smoking behaviors, including heaviness of smoking and smoking cessation, are known to be under a degree of genetic influence. The enzyme catechol O-methyltransferase (COMT) is of relevance in studies of smoking behavior and smoking cessation due to its presence in dopaminergic brain regions. While the COMT gene is therefore one of the more promising candidate genes for smoking behavior, some inconsistencies have begun to emerge.
We explored whether the rs4680 A (Met) allele of the COMT gene predicts increased heaviness of smoking and reduced likelihood of smoking cessation in a large population-based cohort of pregnant women. We further conducted a meta-analysis of published data from community samples investigating the association of this polymorphism with heaviness of smoking and smoking status.
In our primary sample, the A (Met) allele was associated with increased heaviness of smoking before pregnancy but not with the odds of continuing to smoke in pregnancy either in the first trimester or in the third trimester. Meta-analysis also indicated modest evidence of association of the A (Met) allele with increased heaviness of smoking but not with persistent smoking.
Our data suggest a weak association between COMT genotype and heaviness of smoking, which is supported by our meta-analysis. However, it should be noted that the strength of evidence for this association was modest. Neither our primary data nor our meta-analysis support an association between COMT genotype and smoking cessation. Therefore, COMT remains a plausible candidate gene for smoking behavior phenotypes, in particular, heaviness of smoking.
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