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.
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: Florence P Varodayan; Michal Bajo; Neeraj Soni; George Luu; Samuel G Madamba; Paul Schweitzer; Marisa Roberto Journal: Addict Biol Date: 2016-01-20 Impact factor: 4.280
Authors: Andrzej Wasilewski; Urszula Lewandowska; Paula Mosinska; Cezary Watala; Martin Storr; Jakub Fichna; Thangam Venkatesan Journal: Am J Gastroenterol Date: 2017-03-28 Impact factor: 10.864
Authors: Rohan H C Palmer; John E McGeary; Valerie S Knopik; L Cinnamon Bidwell; Jane M Metrik Journal: Am J Drug Alcohol Abuse Date: 2019-06-11 Impact factor: 3.829
Authors: Kathleen A Brown-Rice; Jamie L Scholl; Kelene A Fercho; Kami Pearson; Noah A Kallsen; Gareth E Davies; Erik A Ehli; Seth Olson; Amy Schweinle; Lee A Baugh; Gina L Forster Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2017-09-20 Impact factor: 5.067
Authors: Daniela Navarro; Ani Gasparyan; Francisco Navarrete; Abraham B Torregrosa; Gabriel Rubio; Marta Marín-Mayor; Gabriela B Acosta; Maria Salud Garcia-Gutiérrez; Jorge Manzanares Journal: Int J Mol Sci Date: 2022-04-26 Impact factor: 6.208