title: Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are jointly associated with preeclampsia.
abstract: This study determined whether genetic variability in exons 3 and 4 of the microsomal epoxide hydrolase gene jointly modifies individual preeclampsia risk. The study also determined whether genetic variability in the gene encoding for microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of preeclampsia. The study involved 133 preeclamptic 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 preeclamptic and control groups. 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 preeclamptic and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization (EM) algorithm. Single-point allele and genotype distributions in exons 3 and 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 T-A (Tyr113-His139) among the preeclampsia group vs the control group (P=0.01). The odds ratio for preeclampsia associated with the high-activity haplotype T-A (Tyr113-His139) was 1.61 (95% CI: 1.12-2.32). The use of two intragenic SNPs jointly in haplotype analysis of association demonstrated that the genetically determined high-activity haplotype T-A (Tyr113-His139) was significantly associated with preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University and University Hospital, Kuopio, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Laasanen
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: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
mesh_terms: D000328:Adult; D001483:Base Sequence; D015992:Body Mass Index; D017931:DNA Primers; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000201:enzymology / Q000235:genetics*; D011247:Pregnancy; D012016:Reference Values
chemical_list: D017931:DNA Primers; D004851:Epoxide Hydrolases