|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|
|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|
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.
|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|
|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
|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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