Association of the DRD2 TaqIA, 5-HT1B A-161T, and CNR1 1359 G/A polymorphisms with alcohol dependence

Abstract

Objective: Alcohol dependence is associated with genetic variants of alcohol-metabolizing enzymes and genes related to dopaminergic, gamma-aminobutyric acidergic, glutamatergic, opioid, cholinergic, and serotonergic systems. Genetic variations in the endogenous cannabinoid system are also involved in alcohol dependence. The present study aimed to evaluate the association between three polymorphisms, DRD2 TaqIA, 5-HT1B A-161T and CNR1 1359 G/A (rs1049353), and alcohol dependence. Methods: One hundred twenty three patients, who were diagnosed as having alcohol dependence according to the DSM-IV criteria and 125 healthy volunteers, were included in the study. With written informed consent, a blood sample was drawn from each individual. Venous blood samples were collected in ethylenediaminetetra acetic acid (EDTA) containing tubes. DNA was extracted from whole blood by the salting out procedure. Genetic analyses were performed as described in the literature by using a Polymerase Chain Reaction method. SPSS 17.0 software was used for statistical analysis. Results: The DRD2 TaqIA polymorphism was analyzed in the study and control groups. In the study group, the A1/ A1 genotype was observed in 5 (4.0%) patients, the A1/ A2 genotype was observed in 51 (41.5%) patients and the A2/A2 genotype was observed in 67 (54.5%) patients. In the control group, the A1/A1 genotype was observed in 6 (4.8%) subjects, the A1/A2 genotype was observed in 40 (32.0%) subjects and the A2/A2 genotype was observed in 79 (62.2%) subjects. For the 5-HT1B receptor A-161T gene polymorphism, the A/A genotype was detected in 61 (49.6%) patients, the A/T genotype was detected in 53 (43.1%) and the T/T genotype was detected in 9 (7.3%) patients. In the control group, the A/A genotype was detected in 84 (67.2%) subjects, the A/T genotype was detected in 39 (31.2%) subjects, and the T/T genotype was detected only in 2 (1.6%) subjects. The G/G genotype was the most common genotype in both study and control groups for CNR1 1359 gene polymorphism. It was detected in 75 (61.0%) study patients and in 84 (67.2%) control subjects. The G/A genotype was observed in 39 (31.7%) patients of the study group and 38 (30.4%) subjects of the control group. The A/A genotype was the most rare genotype in both groups; it was detected only in 9 (7.3%) study patients and 3 (2.4%) control subjects. Of the three polymorphisms investigated, 5-HT1B A-161T was the only one found to be associated with alcohol dependence. Conclusions: The 5-HT1B receptor A-161T polymorphism might be a promising marker for alcohol dependence; however, future studies are needed to clarify these findings.