Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study.
BACKGROUND
Dopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three single nucleotide polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian subjects.


METHODS
In a retrospective analysis, genetic association of three polymorphisms from DRD2 gene with alcohol dependence was investigated using a case-control approach. Alcohol dependence was determined by DSM-IV criteria and a total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were recruited. Odds ratio and confidence interval was calculated to determine risk conferred by a predisposing allele/genotype/haplotype. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair-wise interactions between SNPs.


RESULTS
The study showed a significant association of -141C Ins allele and a trend of association of TaqI A1 allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins and TaqI A1 alleles (-141C Ins-A-A1) seems to confer approximately 2.5 times more risk to develop alcohol dependence.


CONCLUSIONS
The study provides preliminary insight into genetic risk to alcohol dependence in Indian males. Two polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical implications among Indian alcoholic subjects.
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi, India.
Pushplata
P
Prasad
Atul
A
Ambekar
Meera
M
Vaswani
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors
D017448:Receptors, Dopamine D2