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Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population.

ABSTRACT: OBJECTIVE:Cholinergic nicotinic receptor (CHRN) gene family has been known to mediate the highly additive effects of nicotine in the body, and implicated nicotine dependence (ND) and related phenotypes. Previous studies have found that CHRNA6-CHRNB3 cluster polymorphisms were significantly associated with the risk of ND and various tobacco behaviors. The aim of study was to evaluate the genetic association of CHRNB3 and CHRNA6 polymorphisms with the risk of ND based on the Fagerstrom Test for Nicotine Dependence (FTND) score and five subscales of nicotine dependence syndrome scale (NDSS) in Korean population. METHODS:Six SNPs in CHRNA6-CHRNB3 cluster were analyzed in 576 Korean subjects. Association analysis using logistic models and regression analysis with NDSS were performed. RESULTS:There was no association in the case-control analysis, whereas all six SNPs were significantly associated with drive factor among NDSS in subgroup based on the FTND score. CHRNB3 rs4954 and CHRNA6 rs16891604 showed significant associations with NDSSF1 (drive) in dominant models among moderate to severe ND among smokers after correction (p(corr) =0.02 and 0.001, respectively), whereas other four SNPs showed significant associations among mild ND after correction (p(corr) =0.03-0.02 in dominant model). CONCLUSION:This study showed that the genetic influence of CHRNB3-CHRNA6 cluster polymorphisms are found in a ND endophenotype (drive) using NDSS subscales, rather than the risk of ND in Korean population. Our findings might be the first report for the association of CHRNB3-CHRNA6 cluster with ND-related phenotypes in Korean and might offer an approach to elucidating the molecular mechanisms of ND and ND-related phenotypes.

SUBMITTER: Won WY

PROVIDER: S-EPMC4124190 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population.

Won Wang-Youn WY Park ByungLae B Choi Sam-Wook SW Kim LyoungHyo L Kwon Min M Kim Jae-Hwa JH Lee Chang-Uk CU Shin Hyoung Doo HD Kim Dai-Jin DJ

Psychiatry investigation 20140721 3

<h4>Objective</h4>Cholinergic nicotinic receptor (CHRN) gene family has been known to mediate the highly additive effects of nicotine in the body, and implicated nicotine dependence (ND) and related phenotypes. Previous studies have found that CHRNA6-CHRNB3 cluster polymorphisms were significantly associated with the risk of ND and various tobacco behaviors. The aim of study was to evaluate the genetic association of CHRNB3 and CHRNA6 polymorphisms with the risk of ND based on the Fagerstrom Tes ...[more]

PMID: 25110504

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Project description:Cigarette smoking is a leading cause of preventable death throughout the world. Nicotine, the primary addictive compound in tobacco, plays a vital role in the initiation and maintenance of its use. Nicotine exerts its pharmacological roles through nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits. Besides the CHRNA4, CHRNB2 and CHRNA5/A3/B4 cluster on chromosome 15, which has been investigated intensively, recent evidence from both genome-wide association studies and candidate gene-based association studies has revealed the crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence (ND). These studies demonstrate two distinct loci within this region. The first one is tagged by rs13277254, upstream of the CHRNB3 gene, and the other is tagged by rs4952, a coding single nucleotide polymorphism in exon 5 of that gene. Functional studies by genetic manipulation in mice have shown that ?6*-nAChRs, located in the ventral tegmental area (VTA), are of great importance in controlling nicotine self-administration. However, when the ?6 subunit is selectively re-expressed in the VTA of the ?6(-/-) mouse by a lentiviral vector, the reinforcing property of nicotine is restored. To further determine the role of ?6*-nAChRs in the process of nicotine-induced reward and withdrawal, genetic knock-in strains have been examined, which showed that replacement of Leu with Ser in the 9' residue in the M2 domain of ?6 produces nicotine-hypersensitive mice (?6 L9'S) with enhanced dopamine release. Moreover, nicotine-induced upregulation may be another ingredient in the pathology of nicotine addiction although the effect of chronic nicotine exposure on the expression of ?6-containing receptors is controversial. To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we here present the most recent studies concerning the genetic effects of the CHRNB3-CHRNA6 gene cluster in ND.

Dataset Information

Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population.

Publications

Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population.

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