期刊
PHARMACOGENETICS AND GENOMICS
卷 27, 期 11, 页码 394-401出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0000000000000304
关键词
DNA methylation; dopamine; genetic variation; MAO genes; monoamine oxidase; smoking dependence; warrior gene
资金
- Academy of Finland [118490]
- Juho Vainio Foundation [201210207, 201310170]
- Russian Scientific Fund [16-15-10396]
- Russian Science Foundation [16-15-10396] Funding Source: Russian Science Foundation
- Academy of Finland (AKA) [118490, 118490] Funding Source: Academy of Finland (AKA)
Objective Smoking dependence is the main cause for tobacco-related illnesses. The addiction-causing substance in tobacco, nicotine, acts through the dopamine pathway in the brain, causing several pleasurable experiences through cigarette smoking. Thus, both genetic and epigenetic factors related to dopamine metabolism may play an important role in influencing an individual's smoking behavior. Materials and methods We studied the 1460 C/T variation and the variable number tandem repeat polymorphism in the MAOA gene and A/G variation in intron 13 in the MAOB gene together with four DNA methylation sites in both of these genes in relation to several smoking-related phenotypes in a study population of 1230 Whites of Russian origin. Results The genotypes studied were found to be associated with smoking status in women; the MAOB G variant allele was more prevalent in female smokers than nonsmokers [odds ratio (OR): 2.16, 95% confidence interval (CI): 1.08-4.33], whereas a reverse relation was observed for the MAOA 1460 T-variant allele (OR: 0.44, 95% CI: 0.21-0.91) and variable number tandem repeat low-activity alleles (OR: 0.49, 95% CI: 0.24-0.98). Moreover, the mean methylation values of the CpG sites studied in the MAOA gene were related to smoking behavior in women. Similarly, several methylation patterns in the MAOB gene were associated with a smoking history, with each CpG site showing a remarkable sex dependence. Conclusion Smoking behavior seems to be related to the genetic and epigenetic profile of MAO genes, with considerable individual and sex-related differences. Copyright (C) (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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