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Background  Brain imaging studies and knock-out animal models have derived substantial abetment for dopamine receptor (DR) subtypes as potential candidates in susceptibility to addictive disorders, including alcohol dependence (AD). Various association studies that compared the frequencies of alleles of the dopamine D1, D2, D3 and D4 receptor genes between alcohol dependent and control subjects have produced suggestive results, though some of them are discordant in nature. In the absence of genetic data from Indian population, we evaluated genetic association of three polymorphisms namely rs4532 in  DRD1 , rs6280 in  DRD3  and 120 bp duplication in 1.2 kb upstream region of  DRD4  with AD.    Methods  A total of 90 cases (alcohol dependent males) and 122 age and ethnicity matched healthy male controls were recruited in the study by following DSM-IV criteria. Three polymorphisms, namely rs4532 in  DRD1 , rs6280 in  DRD3  and 120 bp duplication in 1.2 kb upstream region of  DRD4  were selected (based on minor allele frequency and available literature) for genotyping by PCR-RFLP/LP method. Allele and genotype frequencies of these genetic markers were compared using Pearson’s  χ  2  test followed by risk assessment using odds ratio. Statistical analysis of clinical parameters such as AUDIT scores of case subjects was also performed.    Results  Statistically significant associations of polymorphisms in  DRD1  and  DRD4  with alcoholism were found.    Conclusions  Our results underscore that genetic variations in dopamine receptors D1 and D4 may influence genetic predisposition to alcoholism. Unavailability of comparative data from Indian population and small sample size necessitate replication of results in an independent cohort.

Case–control association analysis of Dopamine receptor polymorphisms in alcohol dependence: a pilot study in Indian males