Effect of genotype and methylation of CYP2D6 on smoking behaviour.
Article Details
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Tiili EM, Antikainen MS, Mitiushkina NV, Sukhovskaya OA, Imyanitov EN, Hirvonen AP
Effect of genotype and methylation of CYP2D6 on smoking behaviour.
Pharmacogenet Genomics. 2015 Nov;25(11):531-40. doi: 10.1097/FPC.0000000000000166.
- PubMed ID
- 26287939 [ View in PubMed]
- Abstract
OBJECTIVE: Cigarette smoking is one of the most influential environmental factors affecting the DNA methylation patterns. The addiction-causing substance of tobacco smoke, nicotine, has also shown the potential to alter DNA methylation patterns. However, genetics has a strong influence on DNA methylation patterns, which in turn may affect an individual's smoking behaviour. MATERIALS AND METHODS: We studied eight functional gene variants of one of the most important drug-metabolizing enzymes, CYP2D6, in relation to smoking behaviour in our well-characterized study population consisting of 1230 Whites of Russian origin. In addition, potential associations between methylation levels in a CpG island in the CYP2D6 gene and sex, age, different smoking-related phenotypes and CYP2D6 genotypes were studied. RESULTS: Both age and sex were found to be associated with the methylation level of the CYP2D6 gene. The CYP2D6 methylation pattern also showed high genotype dependence; compared with the extensive metabolizer genotype, the poor metabolizer genotype occurred notably more frequently with higher methylation status (odds ratio 5.05, 95% confidence interval 2.14-11.90). Moreover, higher methylation levels were found to be related inversely to heavier smoking (odds ratio 0.56, 95% confidence interval 0.35-0.91). We also found associations between the CYP2D6 genotype and smoking habits; the poor metabolizer genotype tended to decrease the risk of becoming a heavy smoker compared with the extensive metabolizers, whereas the ultrarapid metabolism-related genotypes tended to increase the risk. CONCLUSION: The CYP2D6-related metabolic capacity seems to be related to cigarette consumption both through genetic and through epigenetic mechanisms.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Nicotine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails