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. 2016 Feb;18(2):196-203.
doi: 10.1093/ntr/ntv049. Epub 2015 Mar 5.

CYP2A6 Longitudinal Effects in Young Smokers

Dale S Cannon  1 , Tait R Medina  2 , Robin J Mermelstein  3 , Donald Hedeker  4 , Amanda V Bakian  5 , Hilary Coon  5 , Edwin H Cook  6 , Cindy Hamil  7 , Robert B Weiss  7
Affiliations

CYP2A6 Longitudinal Effects in Young Smokers

Dale S Cannon et al. Nicotine Tob Res. 2016 Feb.

Abstract

Introduction: 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.

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Figures

Figure 1.
Figure 1.
Predicted number of days smoked by CYP2A6 diplotype predicted rate (CDPR) and time calculated using estimates from Poisson portion of the zero-inflated Poisson growth-curve model predicting DAYS (Supplementary Table S-3, Poisson). Solid line with circle represents Slow CDPR, long-dashed line with diamond represents Intermediate CDPR and short-dashed line with triangle represents Normal CDPR. Predicted number of days smoked was calculated with controls held at their mean value.
Figure 2.
Figure 2.
Predicted probability of smoking discontinuation by CYP2A6 diplotype predicted rate (CDPR) and time calculated using estimates from the logistic portion of the zero-inflated Poisson growth-curve model predicting DAYS (Supplementary Table S-3, Logistic). Solid line with circle represents Slow CDPR, long-dashed line with diamond represents Intermediate CDPR and short-dashed line with triangle represents Normal CDPR. Predicted probability of smoking discontinuation was calculated with controls held at their mean value.
Figure 3.
Figure 3.
Predicted Nicotine Dependence Syndrome Scale (NDSS) score by CYP2A6 diplotype predicted rate (CDPR) and time calculated using estimates from the linear growth-curve model predicting NDSS (Supplementary Table S-3, NDSS). Solid line with circle represents Slow CDPR, long-dashed line with diamond represents Intermediate CDPR and short-dashed line with triangle represents Normal CDPR. Predicted NDSS score was calculated with controls held at their mean value.
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References

    1. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. 2009;49:57–71. 10.1146/annurev.pharmtox.48.113006.094742. - PMC - PubMed
    1. Malaiyandi V, Sellers EM, Tyndale RF. Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Clin Pharmacol Ther. 2005;77(3):145–158. 10.1016/j.clpt.2004.10.011. - PubMed
    1. Ray R, Tyndale RF, Lerman C. Nicotine dependence pharmacogenetics: role of genetic variation in nicotine-metabolizing enzymes. J Neurogenet. 2009;23(3):252–261. 10.1080/01677060802572887. - PMC - PubMed
    1. Thorgeirsson TE, Gudbjartsson DF, Surakka I, et al. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet. 2010;42(5):448–453. 10.1038/ng.573. - PMC - PubMed
    1. Audrain-McGovern J, Al Koudsi N, Rodriguez D, Wileyto EP, Shields PG, Tyndale RF. The role of CYP2A6 in the emergence of nicotine dependence in adolescents. Pediatrics. 2007;119(1):e264–e274. 10.1542/peds.2006-1583. - PubMed

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