The role of CYP2A6 in the emergence of nicotine dependence in adolescents.
OBJECTIVE
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.
Audrain-McGovern
Janet
J
Tobacco Use Research Center, Department of Psychiatry, University of Pennsylvania, 3535 Market St, Philadelphia, PA 19104, USA. audrain@mail.med.upenn.edu
Al Koudsi
Nael
N
Rodriguez
Daniel
D
Wileyto
E Paul
EP
Shields
Peter G
PG
Tyndale
Rachel F
RF
D000293:Adolescent; D000294:Adolescent Behavior; D000428:Alcohol Drinking; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008385:Marijuana Smoking; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D012907:Smoking / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000523:psychology
D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6