title: Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome.
abstract: OBJECTIVE
  To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS).
  
  
  METHODS
  Retrospective case-control study.
  
  
  METHODS
  University-based clinic.
  
  
  METHODS
  One hundred twelve white women with PCOS and 115 healthy controls.
  
  
  METHODS
  None.
  
  
  METHODS
  The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm.
  
  
  RESULTS
  Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8).
  
  
  CONCLUSIONS
  The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Seija
authors.initials: S
authors.lastname: Korhonen
authors.forename: Eeva Liisa
authors.initials: EL
authors.lastname: Romppanen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Maritta
authors.initials: M
authors.lastname: Hippeläinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
mesh_terms: D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D004851:Epoxide Hydrolases