CYP2A6 metabolism in the development of smoking behaviors in young adults

Emily Olfson, Joseph Bloom, Sarah Bertelsen, John P. Budde, Naomi Breslau, Andrew Brooks, Robert Culverhouse, Grace Chan, Li Shiun Chen, David Chorlian, Danielle M. Dick, Howard Edenberg, Sarah Hartz, Dorothy Hatsukami, Victor M. Hesselbrock, Eric O. Johnson, John R. Kramer, Samuel Kuperman, Jacquelyn L. Meyers, John NurnbergerBernice Porjesz, Nancy L. Saccone, Marc A. Schuckit, Jerry Stitzel, Jay A. Tischfield, John P. Rice, Alison Goate, Laura J. Bierut

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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, ≤5minutes) 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.

Original languageEnglish (US)
JournalAddiction Biology
DOIs
StateAccepted/In press - 2016

Fingerprint

Tobacco Use Disorder
Cytochrome P-450 Enzyme System
Young Adult
Smoking
Nicotine
Tobacco Products
Alcoholism
Smoke
Reaction Time
Meta-Analysis
Enzymes

Keywords

  • CYP2A6
  • Genetics
  • Nicotine dependence
  • Smoking
  • Young adults

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Olfson, E., Bloom, J., Bertelsen, S., Budde, J. P., Breslau, N., Brooks, A., ... Bierut, L. J. (Accepted/In press). CYP2A6 metabolism in the development of smoking behaviors in young adults. Addiction Biology. https://doi.org/10.1111/adb.12477

CYP2A6 metabolism in the development of smoking behaviors in young adults. / 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; 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.

In: Addiction Biology, 2016.

Research output: Contribution to journalArticle

Olfson, E, Bloom, J, Bertelsen, S, Budde, JP, Breslau, N, Brooks, A, Culverhouse, R, Chan, G, Chen, LS, Chorlian, D, Dick, DM, Edenberg, H, Hartz, S, Hatsukami, D, Hesselbrock, VM, Johnson, EO, Kramer, JR, Kuperman, S, Meyers, JL, Nurnberger, J, Porjesz, B, Saccone, NL, Schuckit, MA, Stitzel, J, Tischfield, JA, Rice, JP, Goate, A & Bierut, LJ 2016, 'CYP2A6 metabolism in the development of smoking behaviors in young adults', Addiction Biology. https://doi.org/10.1111/adb.12477
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 ; 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. / CYP2A6 metabolism in the development of smoking behaviors in young adults. In: Addiction Biology. 2016.
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AU - Brooks, Andrew

AU - Culverhouse, Robert

AU - Chan, Grace

AU - Chen, Li Shiun

AU - Chorlian, David

AU - Dick, Danielle M.

AU - Edenberg, Howard

AU - Hartz, Sarah

AU - Hatsukami, Dorothy

AU - Hesselbrock, Victor M.

AU - Johnson, Eric O.

AU - Kramer, John R.

AU - Kuperman, Samuel

AU - Meyers, Jacquelyn L.

AU - Nurnberger, John

AU - Porjesz, Bernice

AU - Saccone, Nancy L.

AU - Schuckit, Marc A.

AU - Stitzel, Jerry

AU - Tischfield, Jay A.

AU - Rice, John P.

AU - Goate, Alison

AU - Bierut, Laura J.

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N2 - 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, ≤5minutes) 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.

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