A Case-Control Study of the APELA Gene and Hypertensive Disorders of Pregnancy
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Published on: July 30, 2016
Naomi Shimada1, Tomohiro Nakayama2,3, Hiroshi Umemura2
1Division of Legal Medicine, Department of Social Medicine, Nihon University School of Medicine, 30-1 Ooyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Insights
Genetic variations in the APELA gene may increase the risk of hypertensive disorders of pregnancy (HDPs). A specific haplotype (T-A rs4541465-rs67448487) was more frequent in women with HDPs.
Area of Science:
- Genetics
- Obstetrics
- Cardiovascular Medicine
Background:
- Hypertensive disorders of pregnancy (HDPs) are complex genetic conditions.
- APELA gene mutations in mice cause HDP-like symptoms, suggesting a role in placental development.
Purpose of the Study:
- To investigate the association between HDPs and genetic variations in the human APELA gene.
- To analyze single-nucleotide variants (SNVs) and haplotypes within the APELA gene in relation to HDPs.
Main Methods:
- A case-control study was conducted with 196 HDP patients and 254 controls.
- Six SNVs in the APELA gene were genotyped.
- Haplotype analysis was performed for identified SNVs.
Main Results:
- No significant association was found for individual SNVs in the APELA gene.
- A significant increase in the T-A haplotype (rs4541465-rs67448487) was observed in the HDP group, particularly in cases of gestational hypertension.
Conclusions:
- The APELA gene may contribute to susceptibility to HDPs.
- The T-A haplotype rs4541465-rs67448487 is a potential genetic marker for HDP risk.
Abstract:
Hypertensive disorders of pregnancy (HDPs) are believed to comprise a group of multifactorial genetic diseases. Recently, it was reported that APELA-knockout mice exhibited HDP-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. The aim of the present study is to determine the associations between HDPs and single-nucleotide variants or haplotypes in the human APELA gene through a case-control study. The subjects were 196 pregnant women with HDPs and a control group of 254 women without HDPs. Six single-nucleotide variants (rs2068792, rs13120303, rs4541465, rs13152225, rs78639146, and rs67448487) were selected from the APELA gene region. Although there were no significant differences for each single-nucleotide polymorphism in the case-control study, the frequency of the T-A haplotypes rs4541465-rs67448487 was significantly higher in the HDP group, especially in those with gestational hypertension, than in the control group. The results suggest that the APELA gene may be a disease-susceptibility gene for HDP.
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