Alcoholism-related phenotypes and genetic variants of the CB1 receptor

Abstract.

Objective:

Neurotransmitter release of GABAergic and glutamatergic neurons may be significantly influenced by cannabinoid CB1 receptors located at presynaptic nerve terminals. GABA and glutamate have been reported to be involved in the pathogenesis of severe alcohol withdrawal-induced seizures and delirium tremens. The aim of this study is to test the potential influence of a bi-allelic cannabinoid receptor gene (CNR1) polymorphism (G1359A) on severe alcoholwithdrawal syndromes.

Methods:

Based upon a sample size estimation, 196 subjects meeting DSM IV and ICD10 criteria for alcohol dependence and 210 non-alcoholic controls were recruited for study. CB1 polymorphisms were determined using polymerase chain reaction (PCR). History of alcohol withdrawal-induced delirium tremens, seizures and other alcohol withdrawal-related phenotypes were obtained using the SSAGA (Semi-Structured Assessment of Genetics in Alcoholism). Data were corroborated with information from the inpatients’ clinical files.

Results:

Allele frequencies of the CNR1 G1359A polymorphism were within the range reported by previous studies. After correcting for multiple testing, no association of the A- or G-allele of CNR1 polymorphism with a history of alcohol withdrawal-induced seizures was detected. In addition, no significant relationships with other alcoholism-related phenotypes were found.

Conclusion:

This study failed to confirm an earlier report of a potential role of a CNR1 polymorphism in the pathogenesis of delirium tremens.