title: Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence.
abstract: An alternative promoter producing a novel 5'-untranslated region of cannabinoid receptor mRNA has recently been described in CNR1, the gene encoding the cannabinoid receptor protein. Single nucleotide polymorphisms (SNPs) adjacent to this site were reported to be associated with polysubstance abuse [Zhang et al., 2004]. We examined the association of 4 SNPs (rs6928499, rs806379, rs1535255, rs2023239) in the distal region of intron 2 of CNR1 both with individual substance dependence diagnoses (i.e., alcohol, cocaine, and opioids), as well as with polysubstance dependence. The study samples consisted of European-American (EA) and African-American (AA) subjects with drug and or alcohol dependence (n = 895), and controls (n = 472). Subjects were grouped as polysubstance dependent, opioid dependent, cocaine dependent, cannabis dependent, and alcohol dependent. There was a modest association of marker rs1535255 with alcohol dependence (P = 0.04), though with correction for multiple phenotype comparisons, this effect was not considered statistically significant. These findings fail to replicate the original report of an association between SNPs adjacent to an alternative CNR1 exon 3 transcription start site and polysubstance abuse.
authors.affiliation: Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
authors.forename: Aryeh I
authors.initials: AI
authors.lastname: Herman
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics; D000483:Alleles; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D019966:Substance-Related Disorders / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D043884:Receptor, Cannabinoid, CB1