Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta‐analysis. (25th July 2011)

• Record Type: Journal Article
• Authors: Clarke, Toni‐Kim; Bloch, Paul J.; Ambrose‐Lanci, Lisa M.; Ferraro, Thomas N.; Berrettini, Wade H.; Kampman, Kyle M.; Dackis, Charles A.; Pettinati, Helen M.; O'Brien, Charles P.; Oslin, David W.; Lohoff, Falk W.
• Is Part Of: Addiction biology. Volume 18:Number 4(2013:Jul.)
• Page Start: 702
• Page End: 708
• Publication Date: 2011-07-25
• Subjects: Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/j.1369-1600.2011.00346.x
• Languages: English
• ISSNs: 1355-6215

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <p>Genetic research on cocaine dependence (CD) may help clarify our understanding of the disorder as well as provide insights for effective treatment. As endocannabinoid signaling and dopamine neurotransmission have been shown to be involved in drug reward, genes related to these systems are plausible candidates for susceptibility to CD. The cannabinoid receptor 1 protein regulates both the endocannabinoid and dopaminergic neurobiological systems, and polymorphisms in the cannabinoid receptor gene, <italic>CNR1, </italic> have been associated previously with substance dependence. In this study, we attempt to replicate findings associating <italic>CNR1</italic> with CD in African Americans. Cocaine‐addicted individuals (<italic>n</italic> = 860) and unaffected controls (<italic>n</italic> = 334) of African descent were genotyped for two single nucleotide polymorphisms (SNPs) in <italic>CNR1</italic> (rs6454674, rs806368). We observed a significant difference in genotype frequencies between cases and controls for both SNPs (<italic>P</italic> ≤ 0.042). A meta‐analysis was also performed combining our data with that of Zuo <italic>et al</italic>. who also studied these polymorphisms in African American cocaine addicts (total <italic>n</italic> = 1253 cases versus 543 controls). When our data were combined, rs6454674 increased in significance to <italic>P</italic> = 0.027; however, rs806368 was no longer significant. This study confirms the association between rs6454674 and CD. However, because there is considerable co‐morbidity of CD with other drugs of abuse, additional studies are necessary to determine whether polymorphisms in <italic>CNR1</italic> induce a general susceptibility to substance dependence or are specific to cocaine addiction. Furthermore, as this population consists of American individuals of African descent, the possibility of population stratification should not be excluded.</p> </abstract>