title: Case-control association analysis of dopamine receptor polymorphisms in alcohol dependence: a pilot study in Indian males.
abstract: 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 χ2 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.
authors.forename: Pushplata
authors.initials: P
authors.lastname: Prasad
authors.forename: Atul
authors.initials: A
authors.lastname: Ambekar
authors.affiliation: National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi 110029, India. meeravaswani@yahoo.com.
authors.forename: Meera
authors.initials: M
authors.lastname: Vaswani
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D020440:Gene Duplication; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: C583260:DRD1 protein, human; C493593:DRD3 protein, human; C493599:DRD4 protein, human; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4