Published online November 27, 2006
PEDIATRICS Vol. 119 No. 1 January 2007, pp. e264-e274 (doi:10.1542/peds.2006-1583)
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ARTICLE

The Role of CYP2A6 in the Emergence of Nicotine Dependence in Adolescents

Janet Audrain-McGovern, PhDa, Nael Al Koudsi, BScb, Daniel Rodriguez, PhDa, E. Paul Wileyto, PhDa, Peter G. Shields, MDc and Rachel F. Tyndale, PhDb

a Tobacco Use Research Center, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania
b Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
c Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC

OBJECTIVES. The objectives of our study were to evaluate whether genetic variation in nicotine metabolic inactivation accounted for the emergence of nicotine dependence from mid- to late adolescence and whether initial smoking experiences mediated this effect.

METHODS. Participants were 222 adolescents of European ancestry who participated in a longitudinal cohort study of the biobehavioral determinants of adolescent smoking. Survey data were collected annually from grade 9 to the end of grade 12. Self-report measures included nicotine dependence, smoking, age first smoked, initial smoking experiences, peer and household member smoking, and alcohol and marijuana use. DNA collected via buccal swabs was assessed for CYP2A6 alleles that are common in white people and are demonstrated to decrease enzymatic function (CYP2A6*2, *4, *9, *12).

RESULTS. Latent growth-curve modeling indicated that normal metabolizers (individuals with no detected CYP2A6 variants) progressed in nicotine dependence at a faster rate and that these increases in nicotine dependence leveled off more slowly compared with slower metabolizers (individuals with CYP2A6 variants). Initial smoking experiences did not account for how CYP2A6 genetic variation impacts nicotine dependence.

CONCLUSIONS. These findings may help to promote a better understanding of the biology of smoking behavior and the emergence of nicotine dependence in adolescents and inform future work aimed at understanding the complex interplay between genetic, social, and psychological factors in adolescent smoking behavior.

Key Words: adolescent smoking • nicotine metabolism • CYP2A6

Abbreviations: ISE—initial smoking experience • SM—slower metabolizer of nicotine • NM—normal metabolizer of nicotine • mFTQ—modified Fagerstrom Tolerance Questionnaire • YRBS—Youth Risk Behavior Survey • LGM—latent growth-curve modeling • CFI—comparative-fit index • RMSEA—root-mean-square error of approximation • SRMR—standardized root-mean residual • HW—Hardy-Weinberg

Accepted Aug 9, 2006.