4G/5G Variant of Plasminogen Activator Inhibitor-1 Gene and Severe Pregnancy-Induced Hypertension: Subgroup Analyses of Variants of Angiotensinogen and Endothelial Nitric Oxide Synthase

Gen Kobashi,The Hokkaido Perinatal Epidemiology ,Kaori Ohta,Hiko Tamashiro,Akira Hata,Hideto Yamada,Noriaki Sakuragi,Seiichiro Fujimoto,Hisanori Minakami

doi:10.2188/jea.je20090003

Abstract

BackgroundPregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3).MethodsAn association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls.ResultsNo significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes.ConclusionsOur findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH.

Highlights

Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality, and is believed to result from both genetic and environmental factors
In a previous study using multivariate analysis, we found that angiotensinogen gene (AGT) T235 and NOS3 Asp[298] were independently associated with PIH, which suggests that these 2 variants are involved in different pathways in the pathogenesis of PIH.[17]
The rate of a positive family history (FH) of hypertension and prepregnancy body mass index (BMI) were significantly higher among cases; there was no significant difference in maternal age or the rates of primigravid and primiparous women between the 2 groups

Summary

Introduction

Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality, and is believed to result from both genetic and environmental factors. PIH can be triggered by placental ischemia, which is caused by an interaction between genetic and environmental factors. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). Methods: An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. With respect to early prediction and prevention of severe PIH, the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH

Methods

Results

Conclusion