与中国男性人群的吸烟行为相关的CYP2A6 和MAOA基因多态性的基因间相互作用
2010/01/07
目的：尼古丁是烟草中的主要精神活性成分，对中枢多巴胺能系统介导的尼古丁刺激奖赏途径引起的依赖起主要作用。因此，在尼古丁代谢和多巴胺分解中的基因多态性可能会影响吸烟行为，它们的相互作用导致风险的调节。在一个基于社区的中国男性人群中研究了细胞色素P450 2A6(CYP2A6)，多巴胺β-羟化酶(DBH), 儿茶酚 邻-甲基转移酶(COMT),和单胺氧化酶A (MAOA)多态性的基因间相互作用与吸烟行为的关联。
方法：在203个目前吸烟者、66个过去吸烟者，和102个从不吸烟者中进行了多态性的基因分型。使用多变量logistic回归模型和多因素减维法来分析关联和多个基因间的相互作用。
结果：具有CYP2A6*1B/CYP2A6*1B基因型的受试者同 CYP2A6*1A/CYP2A6*1A基因型的受试者相比具有增加启始吸烟风险的统计学显著趋势[优势比(OR)=3.5, 95% 可信区间(CI)= 1.5-8.1]，具有CYP2A6*1/CYP2A6*1基因型的受试者 与CYP2A6*4C基因型的受试者相比启始吸烟的风险(OR=2.4, 95% CI=1.2-4.5)和持续吸烟的风险(OR=4.0, 95% CI=1.5-10.3)都是升高的。MAOA 和 CYP2A6基因间相互作用的最佳模型以多因子减维方法来描述（精确度64.11%, P<0.001),提示具有联合MAOA EcoRV的1460 T/O基因型和CYP2A6*1/CYP2A6*1基因型的携带者具有较高的吸烟风险(OR=15.4, 95% CI=4.5-52.5).
结论：本研究发现CYP2A6基因多态性以及与MAOA基因的相互作用参与了中国男性人群的吸烟行为的风险调节。
（张永明编译 刘国梁审校）
Pharmacogenetics &Genomics. 2009 Mar ：6 , Publish Ahead of Print.
Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population.
Tang, Xun a d; Guo, Song b c; Sun, Hongqiang c; Song, Xuemei d; Jiang, Zuonin c; Sheng, Lixiang c; Zhou, Dongfeng b; Hu, Yonghua a d; Chen, Dafang a d
(a)Department of Epidemiology and Biostatistics
(b)Institute of Mental Health, Peking University Health Science Center
(c)National Drug Dependence Treatment Center, Beijing Anding Hospital Affiliated Capital University of Medical Sciences
(d)Key Laboratory of Epidemiology, Ministry of Education, Beijing, China
(b)Institute of Mental Health, Peking University Health Science Center
(c)National Drug Dependence Treatment Center, Beijing Anding Hospital Affiliated Capital University of Medical Sciences
(d)Key Laboratory of Epidemiology, Ministry of Education, Beijing, China
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.
DOI Number 10.1097/FPC.0b013e328329893c
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.
DOI Number 10.1097/FPC.0b013e328329893c
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