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Association of CHRNA4 polymorphisms with smoking behavior in two populations.

ABSTRACT: CHRNA4, the gene that encodes the nicotinic acetylcholine receptor ?(4) subunit, is a potential candidate gene for nicotine dependence (ND). However, studies of the association of CHNRA4 with smoking behavior have shown inconsistent results. Our meta-analysis of linkage studies of smoking behavior identified a genome-wide significant linkage of the phenotype maximum number of cigarettes smoked in a 24-hour period to a region (20q13.12-q13.32) harboring CHRNA4. This motivated us to examine the association of CHRNA4 with smoking behavior in two independent samples. In this study, we examined five single nucleotide polymorphisms (SNPs) within CHRNA4 and three smoking-related behaviors: one quantitative trait [cigarettes smoked per day (CPD)], and two binary traits [DSM-IV diagnosis of ND and dichotomized Fagerstrom test of ND (FTND)], in 1,249 unrelated European-Americans (EAs) and 1,790 unrelated African-Americans (AAs). Using the combined sample with sex, age, and race as covariates, the synonymous SNP rs1044394 was significantly associated with ND (P?=?0.001) and FTND (P?=?0.01). Rs2236196, which has a low correlation with rs1044394, was also significantly associated with CPD (P?=?0.003). The pattern of association for these SNPs was similar in AAs and EAs. After correction for multiple testing, the association between rs1044394 and ND in the combined sample remained significant (P?=?0.033). In summary, our study supports association between CHRNA4 common variation and ND in AA and EA samples. Additional studies will be necessary to evaluate the role of rare variants at CHRNA4 for ND.

SUBMITTER: Han S

PROVIDER: S-EPMC3742073 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Association of CHRNA4 polymorphisms with smoking behavior in two populations.

Han Shizhong S Yang Bao-Zhu BZ Kranzler Henry R HR Oslin David D Anton Raymond R Gelernter Joel J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20110328 4

CHRNA4, the gene that encodes the nicotinic acetylcholine receptor α(4) subunit, is a potential candidate gene for nicotine dependence (ND). However, studies of the association of CHNRA4 with smoking behavior have shown inconsistent results. Our meta-analysis of linkage studies of smoking behavior identified a genome-wide significant linkage of the phenotype maximum number of cigarettes smoked in a 24-hour period to a region (20q13.12-q13.32) harboring CHRNA4. This motivated us to examine the as ...[more]

PMID: 21445957

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Project description:IntroductionSmoking prevalence, cigarettes per day (CPD), and lung cancer incidence differ between Northern Plains (NP) and Southwest (SW) American Indian populations. We used cotinine as a biomarker of tobacco smoke exposure to biochemically characterize NP and SW smokers and nonsmokers and to investigate factors associated with variation in tobacco exposure.MethodsAmerican Indians (N = 636) were recruited from two different tribal populations (NP and SW) as part of a study conducted as part of the Collaborative to Improve Native Cancer Outcomes P50 project. For each participant, a questionnaire assessed smoking status, CPD, second-hand smoke exposure, and traditional ceremonial tobacco use; plasma and/or salivary cotinine was measured.ResultsCotinine levels were (mean ± 95% confidence interval [CI]) 81.6 ± 14.1 and 21.3 ± 7.3 ng/ml among NP smokers and non-mokers, respectively, and 44.8 ± 14.4 and 9.8 ± 5.8 ng/ml among SW smokers and nonsmokers, respectively. Cotinine levels correlated with CPD in both populations (p < .0001). Cotinine ?15 ng/ml was measured in 73.4% of NP smokers and 47.8% of SW smokers and in 19.0% of NP nonsmokers and 10.9% of SW nonsmokers. Ceremonial traditional tobacco use was associated with higher cotinine among NP smokers only (p = 0.004). Second-hand smoke exposure was associated with higher cotinine among NP non-smokers (P < 0.02). More secondhand smoke exposure was associated with smoking more CPD in both populations (p = 0.03-0.29). Linear regression modeling mirrored these findings.ConclusionsHigh prevalence of smoking in the Northern Plains and high cotinine levels among nonsmokers in both regions highlights the tribal populations' risk for tobacco-related disease.ImplicationsThere is a high prevalence of smoking in Northern Plains American Indians. Among Northern Plains and Southwest nonsmokers, relatively high cotinine levels, representative of high tobacco exposure, suggest considerable exposure to second-hand smoke. It is critical to highlight the extent of second-hand smoke exposure among the Northern Plains and Southwest American Indians and to enhance efforts to initiate smoke-free policies in tribal communities, which are not subject to state-level polices.

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Association of CHRNA4 polymorphisms with smoking behavior in two populations.

Publications

Association of CHRNA4 polymorphisms with smoking behavior in two populations.

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