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Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population
Tang, Xun1,4; Guo, Song2,3; Sun, Hongqiang3; Song, Xuemei4; Jiang, Zuonin3; Sheng, Lixiang3; Zhou, Dongfeng2; Hu, Yonghua1,4; Chen, Dafang1,4
关键词catechol O-methyl transferase cytochrome P450 2A6 dopamine beta-hydroxylase gene-gene interaction monoamine oxidase A nicotine metabolism polymorphism smoking
刊名PHARMACOGENETICS AND GENOMICS
2009-05-01
DOI10.1097/FPC.0b013e328329893c
19期:5页:345-352
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
关键词[WOS]CATECHOL-O-METHYLTRANSFERASE ; DOPAMINE METABOLIC ENZYMES ; NICOTINE METABOLISM ; MONOAMINE-OXIDASE ; TOBACCO CONSUMPTION ; CIGARETTE-SMOKING ; ASSOCIATION ; SMOKERS ; METHOXSALEN ; INHIBITION
英文摘要

Objectives Nicotine is the major psychoactive ingredient in tobacco, and is responsible for dependence through the nicotine-stimulated reward pathway mediated by the central dopaminergic system. Consequently, genetic polymorphisms in both nicotine metabolism and dopamine catabolism genes may influence smoking behavior, and interact with each other resulting in risk modulation. In this study, we investigated the association and multilocus gene-gene interactions of cytochrome P450 2A6 (CYP2A6), dopamine beta-hydroxylase (DBH), catechol O-methyl transferase (COMT), and monoamine oxidase A (MAOA) polymorphisms with smoking behavior in a community-based Chinese male population.

Methods The polymorphisms were genotyped in 203 current smokers, 66 former smokers, and 102 never smokers. Multivariate logistic regression models and the multifactor dimensionality reduction method were used to analyze the association and multilocus gene-gene interactions.

Results Statistically significant trends were shown for increased risk of smoking initiation in participants with CYP2A6*1B/CYP2A6*1B genotypes compared with those with CYP2A6*1A/CYP2A6*1A genotypes [odds ratio (OR) = 3.5, 95% confidence interval (CI)= 1.5-8.1], and participants with CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking initiation (OR = 2.4, 95% CI = 1.2-4.5) and smoking persistence (OR = 4.0, 95% CI = 1.5-10.3) than those who have CYP2A6*4C genotypes. Moreover, the best model involved a gene-gene interaction between MAOA and CYP2A6 was characterized by the multifactor dimensionality reduction method (64.11% accuracy, P < 0.001), and indicated that carriers of the combined 1460 T/O genotype for MAOA EcoRV and CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking (OR = 15.4, 95% CI = 4.5-52.5).

Conclusion These findings suggested a substantial influence of CYP2A6 polymorphism as well as the interaction with MAOA resulting in risk modulation on smoking behavior in Chinese male population. Pharmacogenetics and Genomics 19:345-352 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

语种英语
WOS记录号WOS:000265567300004
项目编号2002CB510100 ; 2003AA205070 ; 2002-489
资助机构National Basic Research Program of China ; National High Technology Research and Development Program of China ; Beijing Ministry of Science and Technology
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64065
专题北京大学精神卫生研究所
北京大学基础医学院
北京大学公共卫生学院_流行病与卫生统计学系
北京大学临床肿瘤学院_麻醉科
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Inst Mental Hlth, Beijing 100191, Peoples R China
3.Capital Univ Med Sci, Beijing Anding Hosp, Natl Drug Dependence Treatment Ctr, Beijing, Peoples R China
4.Minist Educ, Key Lab Epidemiol, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Tang, Xun,Guo, Song,Sun, Hongqiang,et al. Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population[J]. PHARMACOGENETICS AND GENOMICS,2009,19(5):345-352.
APA Tang, Xun.,Guo, Song.,Sun, Hongqiang.,Song, Xuemei.,Jiang, Zuonin.,...&Chen, Dafang.(2009).Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population.PHARMACOGENETICS AND GENOMICS,19(5),345-352.
MLA Tang, Xun,et al."Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population".PHARMACOGENETICS AND GENOMICS 19.5(2009):345-352.
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