CYP2A6 metabolism in the development of smoking behaviors in young adults.
- Authors
- Olfson, Emily; Bloom, Joseph; Bertelsen, Sarah; Budde, John P; Breslau, Naomi; Brooks, Andrew; Culverhouse, Robert; Chan, Grace; Chen, Li-Shiun; Chorlian, David; Dick, Danielle M; Edenberg, Howard J; Hartz, Sarah; Hatsukami, Dorothy; Hesselbrock, Victor M; Johnson, Eric O; Kramer, John R; Kuperman, Samuel; Meyers, Jacquelyn L; Nurnberger, John; Porjesz, Bernice; Saccone, Nancy L; Schuckit, Marc A; Stitzel, Jerry; Tischfield, Jay A; Rice, John P; Goate, Alison; Bierut, Laura J
- Year
- 2018
- Journal
- Addiction biology
- PMID
- 28032407
- DOI
- 10.1111/adb.12477
- PMCID
- PMC5491369
Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.
Primary COGA sample selection.
Association between predicted metabolism and smoking behaviors in two studies of European American young adult daily smokers. Error bars reflect standard errors adjusted for sample size.
A theoretical framework of the development of smoking behaviors in relation to CYP2A6 variation. Steps 1 and 2 are supported by this paper and previous studies. Steps 3 and 4 are supported by previous studies (reviewed in Benowitz, 2008; Malaiyandi et al., 2005)
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Individual variations in motives for nicotine self-administration in male rats: evidence in support for a precision psychopharmacology. | Garcia-Rivas V et al. | — | 2024 | → |
| Evidence of individual differences in motives for nicotine seeking in classical nicotine self-administration and associated outcomes of varenicline administration | Garcia-Rivas V et al. | — | 2021 | — |
| Impact of CYP2A6 Activity on Nicotine Reinforcement and Cue-Reactivity in Daily Smokers. | Butler K et al. | — | 2021 | → |
| Cytochrome P450 2A6 whole-gene deletion (CYP2A6*4) polymorphism reduces risk of lung cancer: A meta-analysis. | Johani FH et al. | — | 2020 | → |
| Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity. | El-Boraie A et al. | — | 2020 | → |
| Neurogenetic determinants and mechanisms of addiction to nicotine and smoked tobacco. | Sharp BM et al. | — | 2019 | → |
| Item Response Theory analysis of Fagerström Test for Cigarette Dependence. | Svicher A et al. | — | 2018 | → |