Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers.
- Authors
- Chenoweth, Meghan J; Sylvestre, Marie-Pierre; Contreras, Gisele; Novalen, Maria; O'Loughlin, Jennifer; Tyndale, Rachel F
- Year
- 2016
- Journal
- Drug and alcohol dependence
- PMID
- 26644138
- DOI
- 10.1016/j.drugalcdep.2015.11.017
- PMCID
- PMC4698159
BACKGROUND: Smoking is influenced by genetic factors including variation in CYP2A6 and CYP2B6, which encode nicotine-metabolizing enzymes. In early adolescence, CYP2A6 slow nicotine metabolism was associated with higher dependence acquisition, but reduced cigarette consumption. Here we extend this work by examining associations of CYP2A6 and CYP2B6 with tobacco dependence acquisition in a larger sample of smokers followed throughout adolescence. METHODS: White participants from the Nicotine Dependence in Teens cohort that had ever inhaled (n=421) were followed frequently from age 12-18 years. Cox's proportional hazards models compared the risk of ICD-10 tobacco dependence acquisition (score 3+) for CYP2A6 and CYP2B6 metabolism groups. Early smoking experiences, as well as amount smoked at end of follow-up, was also computed. At age 24 (N=162), we assessed concordance between self-reported cigarette consumption and salivary cotinine. RESULTS: In those who initiated inhalation during follow-up, CYP2A6 slow (vs. normal) metabolizers were at greater risk of dependence (hazards ratio (HR)=2.3; 95% CI=1.1, 4.8); CYP2B6 slow (vs. normal) metabolizers had non-significantly greater risk (HR=1.5; 95% CI=0.8, 2.6). Variation in CYP2A6 or CYP2B6 was not significantly associated with early smoking symptoms or cigarette consumption at end of follow-up. At age 24, neither gene was significantly associated with dependence status. Self-reported consumption was associated with salivary cotinine, a biomarker of tobacco exposure, acquired at age 24 (B=0.37; P<0.001). CONCLUSIONS: Our findings extend previous work indicating that slow nicotine metabolism mediated by CYP2A6, and perhaps CYP2B6, increases risk for tobacco dependence throughout adolescence.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| CYP2A6 metabolism in the development of smoking behaviors in young adults. | 2018 | 28032407 |
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