Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population

Department of Epidemiolgy and Biostatistics, Peking University Health Science Center, Peking, China.
Pharmacogenetics and Genomics (Impact Factor: 3.48). 05/2009; 19(5):345-52. DOI: 10.1097/FPC.0b013e328329893c
Source: PubMed


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.
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.
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).
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.

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    • "Liu and colleagues found reduced metabolic function of CYP2A6 in Chinese smokers that was associated with fewer cigarettes smoked, a later initiation of smoking regularly, a shorter duration of smoking, and a lower likelihood of smoking cessation.[116] Tang and colleagues reported on the interaction between CYP2A6 polymorphism and MAOA in risk modulation of smoking behavior (i.e., smoking initiation and smoking persistence) in a Chinese male population.[117] Chinese scientists have also identified important associations between genetic polymorphism of the CYP450 enzyme gene with the concomitant diseases of substance abuse disorders and with the dosage and side effects of pharmacological treatments for substance abuse disorders.[49],[118],[119] "
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    • "In addition to the CGASP result mentioned above, several other studies have reported interesting results from the joint analysis of multiple loci chr15q25 in samples of European descent (Li et al. 2010a; Liu et al. 2010; Thorgeirsson et al. 2010; Tobacco and Genetics Consortium 2010), African Americans (Li et al. 2010a), and Koreans (Li et al. 2010b). Additional joint genetic effects related to smoking have been reported in other candidate regions, including interactions among variants in GABBR1 and GABBR2 related to nicotine dependence in African and European Americans (Li et al. 2009) and an interaction between CYP2A6 and MAOA affecting smoking in Chinese (Tang et al. 2009). "
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