Article

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: 3.45). 05/2009; 19(5):345-52. DOI: 10.1097/FPC.0b013e328329893c
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
154 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Addiction is a complex disease affecting the central nervous system, and consists of a set of characteristic symptoms and signs. The origin of addiction is multifactorial. In this article, we addresses three aspects: 1) knowledge bases related to chemical substances in cigarette smoke, 2) process the neurobiology of nicotine addiction, and 3) a review of recent literature about genetic association studies in the addictive process and related phenotypic traits. Regarding the literature review, was used the search tool based from the National Center for Biotechnology Information (NCBI) of the United States, the key words used were Nicotine, Smoking, Dependence, Genetic, Tobacco, Neurobiology and GWAS. The revised publication period was from January 2005 to July 2010. In conclusion, there are abundant studies which demonstrate that the genetic component contributes to a large proportion of the risk of developing addiction to nicotine, thus generating new knowledge on genes or genome regions that had not previously been described in the addiction process and now become a new field of scientific exploration.
    Neumologia y cirugía de tórax 07/2011; 70(3):179-187..
  • [Show abstract] [Hide abstract]
    ABSTRACT: A relatively simple test set-up assists in the broadband tuning of circuits operating at high power levels (i.e. 30 Watts). This procedure also employs a fairly common equipment set. With this method it is possible to optimize ¿in (reflection coefficient) as well as Gp (power gain) across the frequency band of interest. This technique employs a network analyzer, which displays ¿in or Gp, allowing the effects of circuit tuning to be observed in real time. This dramatically reduces the time it takes to optimize circuit performance. ¿in data includes phase information, which can reduce circuit losses seen when transforming past 50 Ohms. This method also allows the user to extend the measurement reference plane into the input matching network.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The importance of genetic factors in substance addiction has long been established. The rationale for this work is that understanding of the function of addiction genes and delineation of the key molecular pathways of these genes would enhance the development of novel therapeutic targets and biomarkers that could be used in the prevention and management of substance abuse. Over the past few years, there has been a substantial increase in the number of genetic studies conducted on addiction in China; these studies have primarily focused on heroin, alcohol, and nicotine dependence. Most studies of candidate genes have concentrated on the dopamine, opioid, and serotonin systems. A number of genes associated with substance abuse in Caucasians are also risk factors in Chinese, but several novel genes and genetic risk factors associated with substance abuse in Chinese subjects have also been identified. This paper reviews the genetic studies of substance abuse performed by Chinese researchers. Genotypes and alleles related to addictive behavior in Chinese individuals are discussed and the contributions of Chinese researchers to the international corpus of knowledge about the genetic understanding of substance abuse are described.
    08/2013; 25(4):199-211. DOI:10.3969/j.issn.1002-0829.2013.04.002