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 J Edenberg; Sarah Hartz; Dorothy Hatsukami; Victor M Hesselbrock; Eric O Johnson; John R Kramer; Samuel Kuperman; Jacquelyn L Meyers; John Nurnberger; Bernice Porjesz; Nancy L Saccone; Marc A Schuckit; Jerry Stitzel; Jay A Tischfield; John P Rice; Alison Goate; Laura J Bierut

doi:10.1111/adb.12477

Back

CYP2A6 metabolism in the development of smoking behaviors in young adults

Journal article

Open access

Peer reviewed

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, …

Addiction biology, Vol.23(1), pp.437-447

01/2018

DOI: 10.1111/adb.12477

PMCID: PMC5491369

PMID: 28032407

Files and links (1)

url

https://soar.suny.edu/bitstream/20.500.12648/8067/1/nihms845149.pdfView

Open Access

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, ≤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.

Adult

Cigarette Smoking - genetics

Cytochrome P-450 CYP2A6 - genetics

European Continental Ancestry Group - genetics

Female

Humans

Male

Odds Ratio

Polymorphism, Single Nucleotide

Tobacco Use Disorder - genetics

Young Adult

Details

Title: Subtitle: CYP2A6 metabolism in the development of smoking behaviors in young adults
Creators: Emily Olfson - Yale University
Joseph Bloom - Washington University in St. Louis
Sarah Bertelsen - Icahn School of Medicine at Mount Sinai
John P Budde - Washington University in St. Louis
Naomi Breslau - Michigan State University
Andrew Brooks - Rutgers, The State University of New Jersey
Robert Culverhouse - Washington University in St. Louis
Grace Chan - University of Connecticut
Li-Shiun Chen - Washington University in St. Louis
David Chorlian - SUNY Downstate Health Sciences University
Danielle M Dick - Virginia Commonwealth University
Howard J Edenberg - Indiana University
Sarah Hartz - Washington University in St. Louis
Dorothy Hatsukami - University of Minnesota
Victor M Hesselbrock - University of Connecticut
Eric O Johnson - RTI International
John R Kramer - University of Iowa
Samuel Kuperman - University of Iowa
Jacquelyn L Meyers - SUNY Downstate Health Sciences University
John Nurnberger - Indiana University
Bernice Porjesz - SUNY Downstate Health Sciences University
Nancy L Saccone - Washington University in St. Louis
Marc A Schuckit - University of California San Diego Medical Center
Jerry Stitzel - University of Colorado Boulder
Jay A Tischfield - Rutgers, The State University of New Jersey
John P Rice - Washington University in St. Louis
Alison Goate - Icahn School of Medicine at Mount Sinai
Laura J Bierut - Washington University in St. Louis
Resource Type: Journal article
Publication Details: Addiction biology, Vol.23(1), pp.437-447
DOI: 10.1111/adb.12477
PMID: 28032407
PMCID: PMC5491369
NLM abbreviation: Addict Biol
ISSN: 1355-6215
eISSN: 1369-1600
Grant note: R25 MH077823 / NIMH NIH HHS K01 DA037914 / NIDA NIH HHS UL1 TR002345 / NCATS NIH HHS TL1 TR000449 / NCATS NIH HHS U10 AA008401 / NIAAA NIH HHS K08 DA032680 / NIDA NIH HHS T32 GM007200 / NIGMS NIH HHS UL1 TR000448 / NCATS NIH HHS F30 AA023685 / NIAAA NIH HHS K02 AA018755 / NIAAA NIH HHS P30 CA091842 / NCI NIH HHS P01 CA089392 / NCI NIH HHS R01 DA036583 / NIDA NIH HHS
Language: English
Date published: 01/2018
Academic Unit: Psychiatry
Record Identifier: 9984293653902771

Metrics

59 Record Views

6 Times Cited - Web of Science