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
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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- "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). "
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. This article is protected by copyright. All rights reserved.Genes Brain and Behavior 06/2015; DOI:10.1111/gbb.12226 · 3.51 Impact Factor
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- "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. "
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.Nicotine & Tobacco Research 02/2011; 13(2):55-63. DOI:10.1093/ntr/ntq209 · 2.81 Impact Factor
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- "Numerous heritable factors (e.g. DRD4 (McClernon et al., 2007), DRD2 (Radwan et al., 2007), COMT (Beuten et al., 2006; Guo et al., 2007), etc) also clearly influence nicotine dependence. "
ABSTRACT: Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerström Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.NeuroImage 01/2011; 54(1):42-8. DOI:10.1016/j.neuroimage.2010.08.008 · 6.36 Impact Factor