Cannabinoid receptor 1 gene association with nicotine dependence

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 Fagerstrom 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: Fagerstrom 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.