Low-activity haplotype of the microsomal epoxide hydrolase gene is protective against placental abruption.
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.
Toivonen
Sari
S
Department of Obstetrics and Gynaecology, Kuopio University and University Hospital, Kuopio, Finland.
Romppanen
Eeva-Liisa
EL
Hiltunen
Mikko
M
Helisalmi
Seppo
S
Keski-Nisula
Leea
L
Punnonen
Kari
K
Heinonen
Seppo
S
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
D004851:Epoxide Hydrolases