title: Cannabinoid receptor 1 gene is associated with alcohol dependence.
abstract: BACKGROUND
  Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD.
  
  
  METHODS
  Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility.
  
  
  RESULTS
  We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009).
  
  
  CONCLUSIONS
  Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcos
authors.forename: Isabel
authors.initials: I
authors.lastname: Pastor
authors.forename: Cristina
authors.initials: C
authors.lastname: de la Calle
authors.forename: Laura
authors.initials: L
authors.lastname: Barrio-Real
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Laso
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology*; D000465:Algorithms; D000483:Alleles; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012044:Regression Analysis; D013030:Spain / Q000453:epidemiology
chemical_list: D043884:Receptor, Cannabinoid, CB1; D004247:DNA