title: Candidate genes for alcohol dependence: A genetic association study from India.
abstract: OBJECTIVE
  Search for candidate genes for alcohol dependence (AD) has been inconsistent and inconclusive. Moreover, most of the research has been confined to a few specific ethnic groups. Hence, the aim of our study was to explore specific candidate genes for AD in north Indian male population.
  
  
  METHODS
  In this clinic-based genetic association study, 210 males with AD and 200 controls matched for age, gender and ethnicity were recruited from the clinic and the general population, respectively. Cases were diagnosed with Semi-structured Assessment for Genetics of Alcoholism-II (SSAGA-II). Single-nucleotide polymorphism genotyping was done by real-time quantitative-polymerase chain reaction (PCR) using Taq Man assay (ABI 7500) fast real-time PCR system.
  
  
  RESULTS
  Both at the genotypic level and at allelic frequency, Met158 variant of catechol-O-methyl transferase (COMT) showed significant increase in cases as compared to controls. The frequency of heterozygous genotype (A/G) of gamma-aminobutyric acid receptor A1 (GABRA1) was significantly lower in cases as compared to controls. Likewise, for GABRA2, the frequency of homozygous recessive genotype (G/G) was significantly higher in the control group. With respect to the 5-hydroxytryptamine (5HT) transporter long promoter region (5HTTLPR), cholinergic receptor muscarinic (CHRM2) and alcohol dehydrogenase 1B (ADH1B) genes, there was no significant difference between the cases and the controls. Aldehyde dehydrogenase (ALDH2) gene was found to be monomorphic in our study population.
  
  
  CONCLUSIONS
  Our study findings showed COMT polymorphism conferring risk and GABRA polymorphism as a protective genotype for Indian male with AD. Genes for alcohol metabolism, serotonin transporter and cholinergic receptor gene polymorphism were perhaps not contributory to AD for Indian population.
authors.affiliation: Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Malhotra
authors.affiliation: Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Basu
authors.affiliation: Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
authors.affiliation: Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Reliance Industries Limited, Navi Mumbai, India.
authors.forename: Neera
authors.initials: N
authors.lastname: Chugh
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics; D044466:Asian People; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043585:Receptor, Muscarinic M2 / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D012701:Serotonin / Q000235:genetics
chemical_list: C487078:CHRM2 protein, human; C546240:GABRA1 protein, human; C484841:GABRA2 protein, human; D043585:Receptor, Muscarinic M2; D011963:Receptors, GABA-A; D012701:Serotonin; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase