Nicotine dependence pharmacogenetics: role of genetic variation in nicotine-metabolizing enzymes.
paper
Cited
Public
- Authors
- Ray, Riju; Tyndale, Rachel F; Lerman, Caryn
- Year
- 2009
- Journal
- Journal of neurogenetics
- PMID
- 19169923
- DOI
- 10.1080/01677060802572887
- PMCID
- PMC3772540
Nicotine-dependence pharmacogenetics research is an emerging field, and a number of studies have begun to characterize the clinical relevance and predictive power of genetic variation in drug-metabolizing enzymes and drug target genes for response to medication. The present paper focuses on evidence for the role of nicotine-metabolizing enzymes in smoking behavior and response to treatment. Nicotine metabolism is mediated primarily by cytochrome P450 2A6 (CYP2A6). Genetic variation in the CYP2A6 gene has been linked with several smoking behavior phenotypes. Individuals who carry null or reduced activity alleles for CYP2A6 smoke fewer cigarettes per day, are less dependent on nicotine, and may have an easier time quitting smoking. A phenotypic measure of CYP2A6 enzyme activity, defined as the ratio of the nicotine metabolites 3'hydroxycotinine/cotinine, also predicts successful quitting with the transdermal nicotine patch, and counseling alone. Faster metabolizers of nicotine respond more poorly to these treatments; however, they may be excellent candidates for non-nicotine therapies, such as bupropion. Inherited variation in the CYP2B6 enzyme is also associated with response to bupropion treatment and counseling alone for smoking cessation. Inhibition of the CYP2A6 enzyme to slow nicotine metabolism is a promising approach to increase nicotine availability and potentially reduce harm from tobacco smoking.
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| # | Section | Preview |
|---|---|---|
| 20 | IMPLICATIONS FOR MEDICATION DEVELOPMENT | The protective effects of null or reduced activity CYP2A6 alleles on both nicotine dependence and⦠|
| 21 | IMPLICATIONS FOR MEDICATION DEVELOPMENT | and an increase in the latency to light a cigarette, compared to smokers who received placebo plus 4β¦ |
| 22 | TRANSLATION OF GENETICS RESEARCH TO PRACTICE | There are a number of stages of research that are necessary prior to the translation of⦠|
| 23 | TRANSLATION OF GENETICS RESEARCH TO PRACTICE | in genotyping individuals, and subsequent effectiveness of the tailored versus untailored therapy⦠|
| 24 | TRANSLATION OF GENETICS RESEARCH TO PRACTICE | Dissemination of information and enhancements in training of primary care physicians to deliver⦠|
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