title: Low-activity haplotype of the microsomal epoxide hydrolase gene is protective against placental abruption.
abstract: OBJECTIVE
  We wanted to determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the occurrence of placental abruption.
  
  
  METHODS
  The study involved 117 women with placental abruption and 115 healthy control pregnant women who were genotyped for two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Chi-square analysis was used to assess genotype and allele frequency differences between the women with placental abruption and the control group. In addition, single-point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, among the women with placental abruption and the control group. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization algorithm.
  
  
  RESULTS
  Single-point allele and genotype distributions in exons 3 and 4 of the EPHX gene were not statistically different between the groups. However, in the haplotype estimation analysis we observed a significantly decreased frequency of haplotype C-A (His113-His139) among the placental abruption group compared with the control group (P = .007). The odds ratio for placental abruption associated with the low-activity haplotype C-A (His113-His139) was 0.552 (95% confidence interval, 0.358 to 0.851).
  
  
  CONCLUSIONS
  The use of two intragenic SNPs jointly in haplotype analysis of association demonstrated that the genetically determined low-activity haplotype C-A (His113-His139) was significantly less frequent in women with placental abruption.
authors.affiliation: Department of Obstetrics and Gynaecology, Kuopio University and University Hospital, Kuopio, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Toivonen
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: Leea
authors.initials: L
authors.lastname: Keski-Nisula
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
mesh_terms: D000037:Abruptio Placentae / Q000201:enzymology* / Q000235:genetics*; D000328:Adult; D000483:Alleles; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: D004851:Epoxide Hydrolases