title: EPHX1 gene polymorphisms in alcohol dependence and their distribution among the Indian populations.
abstract: BACKGROUND
  The microsomal epoxide hydrolase is a phase II enzyme of the biotransformation. The human epoxide hydrolase 1 (EPHX1) gene lies in the chromosomal region 1q42.1 and exhibits polymorphism. Two single nucleotide polymorphisms (SNPs) have been described in the coding region of the EPHX1 gene that produces two protein variants.
  
  
  METHODS
  A total of 604 samples belonging to 13 Indian populations were included in this study. Based on the DSM-IV criteria, 184 individuals from Kota population were classified into alcoholism cases (100) and controls (84). Genotypes of Tyr113His and His139Arg polymorphisms in the EPHX1 gene were determined using PCR and sequencing. Associations were tested using Pearson's χ(2) test and haplotype analyses.
  
  
  RESULTS
  We found significant association between EPHX1 gene Tyr113His polymorphism and alcoholism in the Kota population (T vs. C: OR = .615, 95% CI = .399-.949, p = .027; TT vs. CC + CT: OR = .536, 95% CI = .297-.969, p = .038). The very slow activity haplotype CA (113His-139His) was also found to be associated with alcohol dependence (p = .048). Analysis of additional populations demonstrated that the Tyr113His polymorphism significantly deviated from Hardy-Weinberg equilibrium in four populations but only one population deviated for the His139Arg locus. All populations shared the four possible two-site haplotypes. Linkage disequilibrium between these two loci was not significant in any of the population studied.
  
  
  CONCLUSIONS
  EPHX1 gene polymorphisms and haplotypes are associated with an increased risk for alcoholism in the Kota population. This is the first report from India that will serve as a template for future investigations of the prevalence of EPHX1 alleles in association with various clinical entities.
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: L V K S
authors.initials: LV
authors.lastname: Bhaskar
authors.forename: K
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Minarbha
authors.initials: M
authors.lastname: Patel
authors.forename: Anish M
authors.initials: AM
authors.lastname: Shah
authors.forename: K
authors.initials: K
authors.lastname: Gopal
authors.forename: L
authors.initials: L
authors.lastname: Saikrishna
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tamang
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
authors.forename: V R
authors.initials: VR
authors.lastname: Rao
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins; D055815:Young Adult
chemical_list: C549604:HEPN1 protein, human; D011506:Proteins; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human