Molecular genetic analysis of preeclampsia

Research Project

Project/Area Number	10470341
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Obstetrics and gynecology
Research Institution	University of Tsukuba
Principal Investigator	KUBO Takeshi Institute of Clinical Medicine, University of Tsukuba Professor, 臨床医学系, 教授 (20010267)
Co-Investigator(Kenkyū-buntansha)	HAMADA Hiromi Institute of Clinical Medicine, University of Tsukuba Assistant Professor, 臨床医学系, 講師 (60261799)
Project Period (FY)	1998 – 1999
Project Status	Completed (Fiscal Year 1999)
Budget Amount *help	¥12,500,000 (Direct Cost: ¥12,500,000) Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000) Fiscal Year 1998: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywords	preeclampsia / multifactorial inheritance / gene polymorphism / candidate gene / plasminogen activator inhibitor-1 / methylenetetrahydrofolate reductase / Nitric Oxide Synthetase
Research Abstract	Preeclampsia contributes to maternal and fetal morbidity and mortality. Causal factors include environmental and inherited components. In this study, we assessed the association between preeclampsia and polymorphisms of the genes that are presumed to be candidate. The polymorphisms analyzed were the 677C/T of the methylenetetrahydrofolate reductase (MTHFR) gene, the 4G/5G of the plasminogen activator inhibitor-1 (PAI-1) gene, the 894G/T and -786T/C of the endothelial nitric oxide synthase gene, the -6G/A of the angiotensinogen gene, the 1691G/A of the blood coagulation factor V gene, and the 20210G/A of the prothrombin gene. The frequency of the homozygotes for the 4G allele of the PAI-1 gene was significantly higher in the patients than in the control pregnant women (p=0.04) or in the healthy volunteers (p=0.02). The 4G allele frequency was also significantly more frequent in the patients than in the control group (p=0.03) and the healthy volunteers group (p=0.02). The genotype homozygous for T677 allele and the T677 allele were significantly increased in the preeclamptic group compared with the control group (p=0.02 and p=0.03, respectively), and compared with the healthy volunteers group (p=0.004 and p=0.02, respectively). There were no associations between preeclampsia and the other gene polymorphisms. Our results suggest that the 4G allele of the PAI-1 gene and the T677 allele of the MTHFR gene are genetic risk factors for preeclampsia.