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CYP2A6 metabolism in the development of smoking behaviors in young adults
Author(s) -
Olfson Emily,
Bloom Joseph,
Bertelsen Sarah,
Budde John P,
Breslau Naomi,
Brooks Andrew,
Culverhouse Robert,
Chan Grace,
Chen LiShiun,
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
Publication year - 2018
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12477
Subject(s) - cyp2a6 , nicotine , nicotine dependence , smoking cessation , medicine , odds ratio , young adult , psychology , physiology , metabolism , demography , cytochrome p450 , cyp1a2 , pathology , sociology
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.