COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers

被引：0
作者：
A I Herman
P I Jatlow
J Gelernter
J B Listman
M Sofuoglu
机构：
[1] Yale University,Department of Psychiatry and VA Connecticut Healthcare System
[2] School of Medicine,Department of Laboratory Medicine
[3] Yale University,undefined
[4] School of Medicine,undefined
来源：
The Pharmacogenomics Journal | 2013年 / 13卷
关键词：
cigarette; genetics; nicotine; pharmacogenetic; smoking;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
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页码：490 / 497
页数：7
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共 275 条
[1]  
Slifstein M(2008)COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET Mol Psychiatry 13 821-827
[2]  
Kolachana B(1958)Enzymatic O-methylation of epinephrine and other catechols J Biol Chem 233 702-705
[3]  
Simpson EH(1966)Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines Pharmacol Rev 18 95-113
[4]  
Tabares P(1996)Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders Pharmacogenetics 6 243-250
[5]  
Cheng B(1999)Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase Annu Rev Pharmacol Toxicol 39 19-52
[6]  
Duvall M(2001)Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia Proc Natl Acad Sci USA 98 6917-6922
[7]  
Axelrod J(2010)Depression and the role of genes involved in dopamine metabolism and signalling Prog Neurobiol 92 112-133
[8]  
Tomchick R(2011)Heterozygosity at catechol-O-methyltransferase Val158Met and schizophrenia: new data and meta-analysis J Psychiatr Res 45 7-14
[9]  
Axelrod J(2010)Are genetic variants of COMT associated with addiction? Pharmacogenet Genomics 20 717-741
[10]  
Lachman HM(2006)Neural mechanisms of addiction: the role of reward-related learning and memory Annu Rev Neurosci 29 565-598
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