D2 dopamine receptor gene and cigarette smoking: A reward gene?

Noble, Ernest P.; Jeor, Sachiko T. St.; Ritchie, Terry; Syndulko, Karl; Fitch, Robert J.; Brunner, Robert L.; Sparkes, Robert S.

doi:10.1016/0306-9877(94)90127-9

Cited by 202 publications

(142 citation statements)

References 24 publications

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“…Smoking status Caucasians Higher frequency of the A1 allele was found among ever smokers 63,64 No association with smoking status (ever, never) 65 No association with smoking status (current, never) 69 No association with smoking status (current smokers versus nonsmokers including former and never smokers) 70 No No association of the TaqI A polymorphism with smoking status was found in female subjects.…”

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

“…58 Some studies, but not all, found the TaqI A1 allele resulted in a lower density of D 2 receptors in the human striatum in vitro and in vivo. [59][60][61][62] The TaqI A1 allele may be a risk factor for a variety of smoking behaviors (Table 2); [63][64][65][66][67][68] however, other studies were not able to replicate these findings. [69][70][71][72][73][74] A meta-analysis did not find an association between the TaqI A1 allele and smoking initiation, smoking persistence, cigarette consumption or cessation.…”

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

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Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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“…Following a report ( Blum et al, 1990 ) that the A1 allele of the Taq1A polymorphism (rs1800497) of the DRD2 gene, a C-T substitution located in a noncoding region of the DRD2 locus, was associated with alcoholism, several studies have investigated the association of this polymorphism with substance use behavior, including tobacco ( Noble et al, 1994 ), opioid ( Lawford et al, 2000 ), and cocaine ( Noble et al, 1993 ) use. Despite the large number of individual studies investigating smoking behavior, however, results have been equivocal, and a recent meta-analysis suggested no evidence of association with cigarette smoking behavior ( M. Munafò, Clark, Johnstone, Murphy, & Walton, 2004 ), although another meta-analysis did suggest evidence of association with risk of alcohol dependence ( M. R. Munafò, Matheson, & Flint, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

Munafò¹,

Timpson²,

David³

et al. 2009

Nicotine &Amp; Tobacco Research

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A number of pharmacogenetic studies have suggested an association between the DRD2 gene and response to smoking cessation pharmacotherapy. Reduced-function alleles (i.e., those associated with, e.g., reduced mRNA expression) of polymorphisms in the DRD2 gene (e.g., Taq1A1) generally have been shown to predict better response to nicotine replacement Abstract Introduction: Many studies have investigated the association of the dopamine type-2 receptor ( DRD2 ) Taq1A polymorphism with tobacco use and cigarette smoking behaviors, but fi ndings remain equivocal. There is a biological basis for considering that this association differs by sex, and differences in subpopulations might explain some of the contradictory evidence.Methods: Our a priori hypothesis was that the association of the DRD2 Taq1A polymorphism with smoking behavior would be more prominent in females than males. We therefore investigated the strength of evidence for an association between the DRD2 Taq1A polymorphism and smoking behavior in a large sample of females and used meta-analytic techniques to synthesize existing published data and explore the role of sex in explaining any heterogeneity between studies. Results:We did not observe any strong evidence of association between the DRD2 Taq1A polymorphism and smoking behavior, including smoking initiation, smoking persistence, and smoking rate, either in our female sample or in our metaanalysis of 29 studies, comprising 28 published studies and the data from the present study. Metaregression suggested an association between the proportion of male participants in a study and the individual study effect size, indicating a larger effect size with a greater proportion of male participants for smoking initiation and smoking persistence. This effect did not appear to be due to the inclusion of the data from the present study.Discussion: Available evidence does not support an association between the DRD2 Taq1A polymorphism and smoking behavior. Contrary to our a priori hypothesis, we found evidence of a stronger association in males than in females.

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“…For example, several studies have reported higher prevalence rates of the TaqI-A1 or TaqI-B1 allele in current and former smokers vs non-smokers. [14][15][16] Pastorelli et al 17 noted that the TaqI-B1 allele was more common among non-alcoholic smokers than the matched non-alcoholic non-smokers. An epidemiological study in Caucasian lung cancer patients reported that ever-smokers had a fourfold increase in the presence of the TaqI-B1 allele compared to never-smokers in both the cancer patients and controls.…”

Section: Introductionmentioning

confidence: 99%

The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms

et al. 2006

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The dopamine receptor D2 (DRD2) gene has polymorphisms that have been linked to regulation of the dopamine system and to an increased prevalence of smoking. The present study examined the relationship of the DRD2 TaqI-A and -B polymorphisms with short-term clinical outcome (abstinence and withdrawal symptoms), collected from daily (14 pre-quit and 42 post-quit) diary data among smokers (n ¼ 116) treated with the nicotine patch plus either venlafaxine or placebo. The results showed that B1/B1 or B1/B2 smokers were slightly less likely to be abstinent on a given day than those homozygous for the TaqI-B2 allele. Significant DRD2 TaqI-B Â time interactions were found for several of the withdrawal scales, indicating that those smokers with the B1/B1 or B1/B2 genotypes tended to report more symptoms over time compared to those with the B2/B2 genotype. No interactions or main effects were found for the DRD2 TaqI-A polymorphism. The findings demonstrate that smokers homozygous for the TaqI-B2 allele experience progressive improvement in self-reported withdrawal symptoms while smokers with the TaqI-B1 allele showing little change.

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D2 dopamine receptor gene and cigarette smoking: A reward gene?

Cited by 202 publications

References 24 publications

Overview of the pharmacogenomics of cigarette smoking

Overview of the pharmacogenomics of cigarette smoking

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms

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