(AAT)n repeat in the cannabinoid receptor gene (CNR1): association with cocaine addiction in an African-Caribbean population

Abstract

Owing to their agonist action on dopaminergic systems, cannabinoids may play a major role in substance dependency and schizophrenia. We examined the (AAT)n triplet repeat polymorphism nearby the CNR1 gene, which encodes human cannabinoid (CB1) receptor, in a male Afro-Caribbean population. The allelic and genotypic distributions were significantly different in non-schizophrenic cocaine dependents (n ¼ 97), schizophrenic cocaine dependents (n ¼ 45) and matched controls (n ¼ 88) (Po10 À4 ). The frequency of the (AAT)12 repeat allele was increased in non-schizophrenic cocaine dependents and schizophrenic cocaine dependents vs controls (25.3 and 26.7 vs 5.7%) (Po10 À4 ). Our results support that the (AAT)n polymorphism nearby the CNR1 gene could be associated with predisposition to cocaine dependency.

Overview of the pharmacogenomics of cigarette smoking

“…Rimonabant, the CB 1 R antagonist, has shown some efficacy in clinical trials for nicotine cessation. 159 Several studies have also found associations of (AAT) n 12-repeat polymorphisms near CNR1, encoding the CB 1 receptor, with increased cocaine dependency 160 but smoking has not been studied directly. A 365 C4A SNP in the gene encoding fatty acid amide hydrolase, the main degradative enzyme for endocannabinoids, decreases enzyme expression and activity.…”

Association Between Single Nucleotide Polymorphisms in the Cannabinoid Receptor Gene (CNR1) and Impulsivity in Southwest California Indians

“…The 1359A/G polymorphism (rs1049353) in the coding exon of CNR1 (exon 4) has also been associated with vulnerability to alcohol withdrawal delirium (Schmidt et al, 2002). Additionally, the rs806380 SNP located in intron 2 of the CNR1 gene was significantly associated with developing one or more cannabis dependence symptoms (Hopfer et al, 2006), and the (AAT)n triplet repeat polymorphism nearby the CNR1 gene was found to be associated with cocaine addiction in an African-Caribbean population (Ballon et al, 2006). However, several studies have also failed to find association of the CNR1 receptor polymorphism and substance dependence phenotypes (Herman et al, 2006;Li et al, 2000;Preuss et al, 2003).…”

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…Furthermore, prior use of cannabis was found to enhance the "high" elicited by subsequent use of cocaine in humans (Foltin et al, 1993;Lukas et al, 1994) and also to hasten relapse in abstinent former cocaine users (Rawson et al, 1986). Furthermore, a recent genetic study found an association between an (AAT)n triplet repeat polymorphism in the CNR1 gene encoding the CB 1 receptor with cocaine addiction in an African-Caribbean population (Ballon et al, 2006). Treatment with HU-210 promoted reinstatement of cocaine-seeking behavior in rats, whereas treatment with SR141716 prevented reinstatement (De Vries et al, 2001).…”