CYP2A6 Longitudinal Effects in Young Smokers.
BACKGROUND
The present study sought to identify time-dependent within-participant effects of CYP2A6 genotypes on smoking frequency and nicotine dependence in young smokers.


METHODS
Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 diplotype predicted rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Growth-curve models characterized baseline and longitudinal CDPR effects with data from eight longitudinal assessments during a 6-year period (from approximately age 16-22) in young smokers of European descent (N = 296, 57% female) who had smoked less than 100 cigarettes lifetime at baseline and more than that amount by Year 6. Phenotypes were number of days smoked during the previous 30 days and a youth version of the Nicotine Dependence Syndrome Scale (NDSS). A zero-inflated Poisson growth-curve model was used to account for the preponderance of zero days smoked.


RESULTS
At baseline, Intermediate CDPR was a risk factor relative to both Normal and Slow CDPR for smoking frequency and the NDSS. Slow CDPR was associated with the highest probability of smoking discontinuation at baseline. However, due to CDPR time trend differences, by young adulthood these baseline effects had been reordered such that the greatest risks for smoking frequency and the NDSS were associated with Normal CDPR.


CONCLUSIONS
Reduced metabolism CYP2A6 genotypes are associated with both risk and protective effects in novice smokers. However, differences in the time-by-CDPR effects result in a reordering of genotype effects such that normal metabolism becomes the risk variant by young adulthood, as has been reliably reported in older smokers.
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT; dale.cannon@hsc.utah.edu.
Dale S
DS
Cannon
Department of Sociology, Indiana University, Bloomington, IN; Institute for Health Research and Policy, University of Illinois, Chicago, IL;
Tait R
TR
Medina
Institute for Health Research and Policy and Psychology Department, University of Illinois, Chicago, IL;
Robin J
RJ
Mermelstein
Department of Health Sciences, University of Chicago, Chicago, IL;
Donald
D
Hedeker
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT;
Amanda V
AV
Bakian
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT;
Hilary
H
Coon
Institute for Juvenile Research, Department of Psychiatry, University of Illinois, Chicago, IL;
Edwin H
EH
Cook
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT.
Cindy
C
Hamil
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT.
Robert B
RB
Weiss
D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D012463:Saliva / Q000378:metabolism; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D016540:Smoking Cessation; D044465:White People / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; D065637:Cytochrome P-450 CYP2A6