Jin Ying, Chen Dafang, Hu Yonghua, Guo Song, Sun Hongqiang, Lu Aili, Zhang Xiaoyan, Li Lingsong
Peking University Stem Cell Research Center, Beijing Anding Hospital Affiliated Capital University of Medical Sciences, China.
Int J Neuropsychopharmacol. 2006 Oct;9(5):557-64. doi: 10.1017/S1461145705006218. Epub 2005 Oct 6.
Monoamine oxidase (MAO) is a critical metabolic enzyme of dopamine, which is a key neurotransmitter of the mesolimbic reward pathway in the human brain. Consequently, the gene encoding MAO is an important candidate gene in the genetics of smoking behaviour. We investigated the association between MAOA polymorphisms (a VNTR polymorphism and an EcoRV polymorphism) and smoking status. A community-based cross-sectional study was conducted with 203 current smoking subjects and 168 non-current smoking subjects in Beijing, China. Genotyping for these polymorphisms was performed using PCR and restriction fragment length polymorphism. Multiple logistic regression models were used to analyse the association of MAOA gene polymorphisms with smoking status. We found that individuals with the 1460T/O genotype had a significantly increased the risk of smoking compared to those with 1460C/O. The adjusted odds ratios (aORs) were 3.2 (95% CI 2.0-5.2) in current vs. non-current smokers group, 1.7 (95% CI 1.1-2.8) in ever vs. never smokers group, 2.5 (95% CI 1.4-4.3) in current vs. never smokers group, and 5.3 (95% CI 2.5-11.2) in current vs. former smokers group respectively. We also found that individuals with the 3-repeat genotype of the VNTR polymorphism had a significantly increased risk of smoking significantly compared to those with the 4-repeat genotype. The aORs were 2.0 (95% CI 1.0-4.1) in the current vs. former smokers group, and 1.9 (95% CI 1.0-3.6) in the nicotine dependent vs. non-nicotine dependent group respectively. Moreover, MAOA gene haplotypes were associated significantly with nicotine dependence in every group. In conclusion, there is an important association between MAOA polymorphisms and smoking status, suggesting a possible role of MAOA gene variants in nicotine dependence.
单胺氧化酶(MAO)是多巴胺的一种关键代谢酶,而多巴胺是人脑中脑边缘奖赏通路的一种关键神经递质。因此,编码MAO的基因是吸烟行为遗传学中的一个重要候选基因。我们研究了MAOA基因多态性(一个可变数目串联重复多态性和一个EcoRV多态性)与吸烟状况之间的关联。在中国北京,对203名当前吸烟者和168名非当前吸烟者进行了一项基于社区的横断面研究。使用聚合酶链反应(PCR)和限制性片段长度多态性对这些多态性进行基因分型。采用多元逻辑回归模型分析MAOA基因多态性与吸烟状况的关联。我们发现,与携带1460C/O基因型的个体相比,携带1460T/O基因型的个体吸烟风险显著增加。在当前吸烟者与非当前吸烟者组中,调整后的比值比(aORs)为3.2(95%可信区间2.0 - 5.2);在曾经吸烟者与从不吸烟者组中,为1.7(95%可信区间1.1 - 2.8);在当前吸烟者与从不吸烟者组中,为2.5(95%可信区间1.4 - 4.3);在当前吸烟者与既往吸烟者组中,分别为5.3(95%可信区间2.5 - 11.2)。我们还发现,与携带4重复基因型的个体相比,携带可变数目串联重复多态性3重复基因型的个体吸烟风险显著增加。在当前吸烟者与既往吸烟者组中,aORs为2.0(95%可信区间1.0 - 4.1);在尼古丁依赖者与非尼古丁依赖者组中,为1.9(可信区间1.0 - 3.6)。此外,MAOA基因单倍型在每组中均与尼古丁依赖显著相关。总之,MAOA基因多态性与吸烟状况之间存在重要关联,提示MAOA基因变异在尼古丁依赖中可能发挥作用。