title: 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.
abstract: BACKGROUND
  Pregnancy-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).
  
  
  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.
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Molecular Biostatistics Research Team, Research Center for Charged Particle Therapy, National Institute of Radiological Science, Chiba, Japan. genkoba@nirs.go.jp
authors.forename: Gen
authors.initials: G
authors.lastname: Kobashi
authors.forename: Kaori
authors.initials: K
authors.lastname: Ohta
authors.forename: Hideto
authors.initials: H
authors.lastname: Yamada
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minakami
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
authors.forename: Hiko
authors.initials: H
authors.lastname: Tamashiro
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D000808:Angiotensinogen; D052250:Nitric Oxide Synthase Type III