DRD1 associations with smoking abstinence across slow and normal nicotine metabolizers

Pharmacogenet Genomics. 2012 Jul;22(7):551-4. doi: 10.1097/FPC.0b013e3283539062.

Abstract

Nicotine metabolism and genetic variation have an impact on nicotine addiction and smoking abstinence; however, further research is required. The nicotine metabolite ratio (NMR) is a robust biomarker of nicotine metabolism used to categorize slow and normal nicotine metabolizers (lower 25th quartile cut off). In two randomized clinical trials of smoking abstinence treatments, we conducted NMR-stratified analyses on smoking abstinence across 13 regions coding for nicotinic acetylcholine receptors and proteins involved in the dopamine reward system. Gene×NMR interaction P-values were adjusted for multiple correlated tests, and we used a Bonferroni-corrected α-level of 0.004 to determine system-wide significance. Three single-nucleotide polymorphisms in DRD1 (rs11746641, rs2168631, and rs11749035) had significant interactions (0.001 ≤ adjusted P-values ≤ 0.004) with increased odds of abstinence within slow metabolizers (odds ratios=3.1-3.5, 95% confidence interval 1.7-6.7). Our findings support the role of DRD1 in nicotine dependence, and identify genetic and nicotine metabolism profiles that may interact to impact nicotine dependence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Humans
  • Linkage Disequilibrium
  • Middle Aged
  • Nicotine / metabolism*
  • Polymorphism, Single Nucleotide
  • Receptors, Dopamine D1 / genetics*
  • Smoking
  • Smoking Cessation
  • Tobacco Use Disorder

Substances

  • Receptors, Dopamine D1
  • Nicotine