Genetic influence of dopamine receptor, dopamine transporter, and nicotine metabolism on smoking cessation and nicotine dependence in a Japanese population.

Masanori Ohmoto,Shinjiro Kobayashi,Yoko Kubota,Tatsuo Takahashi,Yasuhide Mitsumoto

doi:10.1186/s12863-014-0151-2

Masanori Ohmoto, Shinjiro Kobayashi + Show 3 more

Open Access

https://doi.org/10.1186/s12863-014-0151-2

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Journal: BMC genetics	Publication Date: Dec 1, 2014
Citations: 47	License type: CC BY 4.0

Affiliation: Hokuriku University

Abstract

BackgroundThis study investigated whether polymorphisms of the ankyrin repeat and kinase domain containing 1 gene (ANKK1), which is adjacent to the dopamine D2 receptor gene (DRD2), and the dopamine transporter (SLC6A3) and cytochrome P450 2A6 (CYP2A6) genes influence smoking cessation and nicotine dependence in a Japanese population. In 96 current and former smokers, genotyping frequencies for the ANKK1/DRD2 TaqIA, SLC6A3 VNTR, and CYP2A6 polymorphisms were subjected to chi-square analysis, and regression analyses were used to determine the association of the genotypes of current smokers with a Heavy Smoking Index, in addition to evaluating the effect of the subjects’ smoking history on the association.ResultsGenotyping results suggested that nicotine dependence among current smokers homozygous for the SLC6A3 10r allele was lower than that of smokers carrying the minor alleles, and that the CYP2A6 polymorphism might mediate this association. Furthermore, the age at which current smokers began smoking might moderate the association between their genetic polymorphisms and nicotine dependence.ConclusionsThis study provides preliminary findings on the influence of genetic variants on the smoking phenotypes in a Japanese population.

Highlights

This study investigated whether polymorphisms of the ankyrin repeat and kinase domain containing 1 gene (ANKK1), which is adjacent to the dopamine D2 receptor gene (DRD2), and the dopamine transporter (SLC6A3) and cytochrome P450 2A6 (CYP2A6) genes influence smoking cessation and nicotine dependence in a Japanese population
The distributions of the SLC6A3 variable number of tandem repeat (VNTR) and ANKK1/DRD2 TaqIA genotypes in current smokers, former smokers, and all participants did not deviate from Hardy-Weinberg equilibrium (HWE) to any appreciable extent, as determined by chi-squared tests
This study examined whether functional polymorphisms in SLC6A3, ANKK1/DRD2, and CYP2A6 affect smoking cessation and nicotine dependence in a Japanese population

Summary

Introduction

This study investigated whether polymorphisms of the ankyrin repeat and kinase domain containing 1 gene (ANKK1), which is adjacent to the dopamine D2 receptor gene (DRD2), and the dopamine transporter (SLC6A3) and cytochrome P450 2A6 (CYP2A6) genes influence smoking cessation and nicotine dependence in a Japanese population. The TaqIA polymorphism (rs1800497) of the ankyrin repeat and kinase domain containing 1 gene (ANKK1) [3]—adjacent to the dopamine D2 receptor gene (DRD2)—is known to be associated with smoking behaviour. Our meta-analysis revealed a significant effect of ANKK1/DRD2 polymorphisms on smoking cessation, which suggested that Caucasians carrying the A1 allele of the Taq1A polymorphism have a lower probability of smoking cessation than Asians do. It has been reported that the frequency of the A1 allele was higher in Americans (53–75%) than in Asians (11–58%) [9]

Results

Discussion

Conclusion