Cannabinoid receptor 1 gene association with nicotine dependence

Arch Gen Psychiatry. 2008 Jul;65(7):816-24. doi: 10.1001/archpsyc.65.7.816.

Abstract

Context: The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence.

Objective: To test the hypothesis that the CNR1 gene is associated with nicotine dependence.

Design: Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n = 688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry.

Participants: White patients aged 18 to 65 years who met the criteria of inclusion.

Main outcome measures: Fagerström Tolerance Questionnaire and FTND scores.

Results: Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P < .001 and P = .009, respectively).

Conclusion: Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Gene Expression / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptor, Cannabinoid, CB1 / genetics*
  • Tobacco Use Disorder / genetics*
  • Twins / genetics

Substances

  • Receptor, Cannabinoid, CB1