中国男性人群中CYP2A6与MAOA基因多态性对吸烟行为的基因-基因相互作用
Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population.
作者信息
Tang Xun, Guo Song, Sun Hongqiang, Song Xuemei, Jiang Zuonin, Sheng Lixiang, Zhou Dongfeng, Hu Yonghua, Chen Dafang
机构信息
Department of Epidemiolgy and Biostatistics, Peking University Health Science Center, Peking, China.
出版信息
Pharmacogenet Genomics. 2009 May;19(5):345-52. doi: 10.1097/fpc.0b013e328329893c.
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 CYP2A61B/CYP2A61B genotypes compared with those with CYP2A61A/CYP2A61A genotypes [odds ratio (OR)=3.5, 95% confidence interval (CI)= 1.5-8.1], and participants with CYP2A61/CYP2A61 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 CYP2A64C 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 CYP2A61/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.
目的
尼古丁是烟草中的主要精神活性成分，通过由中枢多巴胺能系统介导的尼古丁刺激奖赏通路导致成瘾。因此，尼古丁代谢和多巴胺分解代谢基因中的遗传多态性可能影响吸烟行为，并相互作用导致风险调节。在本研究中，我们调查了细胞色素P450 2A6（CYP2A6）、多巴胺β-羟化酶（DBH）、儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶A（MAOA）基因多态性与中国男性社区人群吸烟行为之间的关联及多位点基因-基因相互作用。
方法
对203名当前吸烟者、66名既往吸烟者和102名从不吸烟者进行基因分型。采用多因素logistic回归模型和多因素降维法分析关联及多位点基因-基因相互作用。
结果
与携带CYP2A61A/CYP2A61A基因型的参与者相比，携带CYP2A61B/CYP2A61B基因型的参与者开始吸烟的风险增加，差异有统计学意义的趋势[比值比（OR）=3.5，95%置信区间（CI）=1.5 - 8.1]，且携带CYP2A61/CYP2A61基因型的参与者开始吸烟（OR=2.4，95% CI=1.2 - 4.5）和持续吸烟（OR=4.0, 95% CI=1.5 - 10.3）的风险高于携带CYP2A64C基因型的参与者。此外，多因素降维法确定的最佳模型涉及MAOA和CYP2A6之间的基因-基因相互作用（准确率64.11%，P<0.001），表明MAOA EcoRV的1460 T/O基因型与CYP2A61/CYP2A6*1基因型组合的携带者吸烟风险更高（OR=15.4，95% CI=4.5 - 52.5）。
结论
这些发现表明CYP2A6基因多态性以及与MAOA的相互作用对中国男性人群吸烟行为的风险调节有重大影响。
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