Molecular genetic analysis of preeclampsia

子痫前期的分子遗传学分析

• 批准号: 10470341
• 负责人: KUBO Takeshi
• 金额: $ 8万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470341/
• 关键词: preeclampsia; multifactorial inheritance; gene polymorphism; candidate gene; plasminogen activator inhibitor-1; methylenetetrahydrofolate reductase; Nitric Oxide Synthetase

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.

先兆子痫有助于母亲和胎儿的发病率和死亡率。原因包括环境和遗传因素。在这项研究中，我们评估了先兆子痫和被认为是候选基因的多态性之间的关联。分析的多态性位点为亚甲基四氢叶酸还原酶（MTHFR）基因677 C/T、纤溶酶原激活物抑制剂-1（派-1）基因4G/5G、内皮型一氧化氮合酶基因894 G/T和-786 T/C、血管紧张素原基因-6 G/A、凝血因子V基因1691 G/A、派-1基因4G等位基因纯合子频率在妊高征组明显高于对照组（p=0.04）和健康对照组（p=0.02）。4G等位基因频率在患者中也显著高于对照组（p=0.03）和健康志愿者组（p=0.02）。与对照组相比（分别为p=0.02和p=0.03），与健康志愿者组相比（分别为p = 0.004和p = 0.02），先兆子痫组中T677等位基因纯合基因型和T677等位基因显著增加。本研究结果提示派-1基因的4G等位基因和MTHFR基因的T677等位基因是子痫前期的遗传危险因素。

项目成果

Yamada N.,Arinami T.,Hamada H.,Kubo T.et al.: "The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia"Journal of Human Genetics. (in press). (2000)

Yamada N.、Arinami T.、Hamada H.、Kubo T.等人：“纤溶酶原激活物抑制剂-1 基因的 4G/5G 多态性与严重先兆子痫相关”人类遗传学杂志。

山田直樹,濱田洋実,他: "内皮型一酸化窒素合成酵素遺伝子多型と妊娠中毒症" 日本妊娠中毒症学会雑誌. 6(in press). (1998)

Naoki Yamada、Hiromi Hamada 等：“内皮一氧化氮合酶基因多态性和先兆子痫”，日本先兆子痫学会杂志 6（出版中）。

Yamada N, Arinami T, Yamakawa-Kobayashi K, Sohda S, Hamada H, Kubo T, Hamaguchi H: "The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia."Journal of Human Genetics. (in press).

Yamada N、Arinami T、Yamakawa-Kobayashi K、Sohda S、Hamada H、Kubo T、Hamaguchi H：“纤溶酶原激活剂抑制剂 1 基因的 4G/5G 多态性与严重先兆子痫相关。”人类遗传学杂志。

Yamada N,Arinami T,Hamada H,Kubo T, et al.: "The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia"Journal of Human Genetics. (in press). (2000)

Yamada N、Arinami T、Hamada H、Kubo T 等人：“纤溶酶原激活物抑制剂 1 基因的 4G/5G 多态性与严重先兆子痫相关”《人类遗传学杂志》。