Document Detail


DRD2 genetic variation in relation to smoking and obesity in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
MedLine Citation:
PMID:  17108814     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Cigarette smoking is the leading cause of morbidity and mortality worldwide. We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence. To assess the specificity of genetic effects, we also investigated other reward-motivated characteristics (obesity, alcohol consumption).
METHODS: Four single nucleotide polymorphisms in DRD2 were genotyped in 2374 participants selected randomly from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. Single nucleotide polymorphism and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals derived from conditional logistic regression models, adjusted for race/ethnicity.
RESULTS: DRD2 polymorphisms were associated with the risk of remaining a current smoker and obesity. Current smokers were more likely than former smokers to possess the variant TaqIA allele (rsmusical sharp1800497) in a dose-dependent model (ORCT=1.2, ORTT=1.5, P for linear trend=0.007). The DRD2 haplotype T-C-T-A [TaqIA(C/T)-957(T/C)-IVS6-83(G/T)- -50977(A/G)] was more common among current than former smokers (OR=1.3, P=0.006), particularly among heavy smokers (21+ cigarettes per day; OR=1.6, P=0.006), and was more common among obese than normal weight individuals (OR=1.4, P=0.02).
CONCLUSIONS: Genetic variation in DRD2 is a modifier of the reward-motivated characteristics, smoking and obesity. As fewer than 15% of smokers who attempt to quit are able to maintain abstinence for greater than 3 months, our results support that DRD2 is an appropriate molecular target for smoking cessation treatments. Our results further support evaluation of DRD2 antagonists for obesity therapies.
Authors:
Lindsay M Morton; Sophia S Wang; Andrew W Bergen; Nilanjan Chatterjee; Paul Kvale; Robert Welch; Meredith Yeager; Richard B Hayes; Stephen J Chanock; Neil E Caporaso
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  16     ISSN:  1744-6872     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-31     Revised Date:  2014-03-25    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  901-10     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Alcohol Drinking / genetics,  psychology
Body Mass Index
Female
Genetic Variation
Haplotypes
Humans
Male
Middle Aged
Obesity / genetics*,  psychology
Polymorphism, Single Nucleotide
Receptors, Dopamine D2 / genetics*
Reward
Smoking / genetics*,  psychology
Smoking Cessation
Tobacco Use Disorder / genetics,  psychology
Chemical
Reg. No./Substance:
0/Receptors, Dopamine D2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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