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Association of a CB1 cannabinoid receptor gene (CNR1) polymorphism with severe alcohol dependence
Lutz G Schmidt1, Jerzy Samochowiec, Ulrich Finckh
1Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, D-55131, Mainz, Germany. schmidt@psychiatrie.klinik.uni-mainz.de
Abstract:
Due to the involvement of the endogenous cannabinoid system in brain reward mechanisms a silent polymorphism (1359G/A; Thr453Thr) in the single coding exon of the CB1 human cannabinoid receptor gene (CNR1) was analysed in 121 severely affected Caucasian alcoholics and 136 most likely non-alcoholic controls. The observed frequency of the A allele was 31.2% for controls and 42.1% for alcoholics with severe withdrawal syndromes (P=0.010). Post-hoc exploration indicated that this allelic association resulted from an excess of the homozygous A/A genotype in patients with a history of alcohol delirium (P=0.031, DF 2), suggesting s an increased risk of delirium (OR=2.45, 95% CI 1.14--5.25). This finding suggests that the homozygous genotype CNR1 1359A/A confers vulnerability to alcohol withdrawal delirium.