Journal of the Society for Gynecologic Investigation

 

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Journal of the Society for Gynecologic Investigation, Vol. 11, No. 8, 540-544 (2004)
DOI: 10.1016/j.jsgi.2004.06.008

Low-Activity Haplotype of the Microsomal Epoxide Hydrolase Gene Is Protective Against Placental Abruption

Sari Toivonen, MD

Eeva-Liisa Romppanen, PhD

Mikko Hiltunen, PhD

Seppo Helisalmi, PhD

Leea Keski-Nisula, MD, PhD

Kari Punnonen, MD, PhD

Departments of Obstetrics and Gynaecology, Clinical Chemistry, Neuroscience and Neurology, and Clinical Genetics, Kuopio University and University Hospital, Kuopio, Finland

Seppo Heinonen, MD, PhD

Departments of Obstetrics and Gynaecology, Clinical Chemistry, Neuroscience and Neurology, and Clinical Genetics, Kuopio University and University Hospital, Kuopio, Finland; Department of Obstetrics and Gynaecology, Kuopio University Hospital, 70211 Kuopio, Finland seppo.heinonen{at}kah.fi

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.

Key Words: Placental abruption • polymorphism • EPHX


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