Association of DRD2 Gene Ser311Cys Polymorphisms, DAT 40bp VNTR and Cannabis Dependence

Abstract

Cannabis as the most widely used illicit drugs among Nigerians has been associated with psychiatric disorders. Studies have implicated genetic predisposition in drug abuse and dependence. We therefore aimed at finding out the relationship between some dopaminergic gene polymorphisms and cannabis dependence.One hundred and four patients attending a psychiatric facility in Lagos, Nigeria who were diagnosed of cannabis dependence according to ICD‐10 were recruited for the study. Ninety six subjects who were not smoking cannabis were also recruited as a comparative group. Genotyping was carried out for Ser311Cys polymorphism of the dopamine receptor D2 (DRD2) gene and the 40bp VNTR of the dopamine transporter (DAT) gene.The Cys allele was more frequent than the Ser allele among the smokers (0.878 and 0.122 respectively), compared to the non‐smokers (0.611 and 0.389 respectively). Most of the smokers were homozygous Cys/Cys (0.433) while most of the non‐smokers were heterozygous Ser/Cys (0.798). Individuals with DRD2 Ser311 allele were more than five times as likely to use cannabis as those with Cys311(p = 0.001, OR = 4.575, 95%CI = 2.727–7.678). The 9 and 10‐repeats (9R and 10R) of the DAT VNTR were the most common repeats. Other repeats were very few and were even found in heterozygous form in combination with either 9 or 10 repeats. The 10R allele was more frequent than the 9R among the smokers (0.560 and 0.440 respectively) and also among the non‐smokers (0.726 and 0.274). While most of the smokers were heterozygous 9R/10R (0.559), most non‐smokers were homozygous 10R/10R (0.595). Individuals with at least one 10R were almost twice as likely to use cannabis as those with the 9R (p = 0.004, OR = 1.915, 95%CI = 1.225 – 2.995).The Cys311 allele of the DRD2 and the 10R of the DAT VNTR were significantly associated with cannabis smoking as individuals with these alleles were more likely to smoke cannabis.