Studies on the genetical and immunological background of the genesis of preeclampsia by analyzing HLA-class II genotype.

通过分析HLA-II类基因型研究子痫前期发生的遗传和免疫学背景。

• 批准号: 10671524
• 负责人: TAKAKUWA Koichi
• 金额: $ 1.73万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-10671524/
• 关键词: preelampsia; HLA; infertility; antiphospholipid antibodies; genetics; immunology; HLA; DNAタイピング

Preeclampsia is a relatively common, yet mysterious, disease in pregnancy, of which the etiology has not yet been fully elucidated. Recently, genetical and immunological factors have been considered to be implicated in the genesis of preeclampsia. The major histocompatibility complex antigen complex of human beings, comprising the human leukocyte antigens (HLA), is useful in examining the immunogenetic basis of some diseases, including preeclampsia. Thus, we analyzed the antigen systems of HLA in patients with preeclampsia using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition to this analysis, we also investigated the association of HLA antigen system with infertility, and the implication of autoantibodies, such as antiphospholipid antibodies, in the genesis of both preeclampsia and infertility. The results obtained in this research project are as follows ;1. The frequency of HLA-DRB1*04 and -DRB1*0403 in patients with preeclampsia, pos … More itive for anticardiolipin antibody, was significantly higher than that in normal fertile women, although the distribution of each HLA-DRB1 genotype was not significantly different between the patients with preeclampsia negative for anticardiolipin antibody and normal fertile women.2. The ferquency of HLA-DRB1*0403 and -DRB1*0410 was significantly higher in patients with infertility positive for anticardiolipin antibody compared with that in normal fertile women, and that of HLA-DQB1*0501 was significantly lower compared with that in normal fertile women.3. The frequency of HLA-DPB1*04 and -DPB1*0402 in patients with unexplained recurrent abortion was significantly higher compared with that in the general population.4. The sera positive for anticardiolipin antibody were observed to show the suppressive effect on the ィイD13ィエD1H-thymidine uptake of human umbilical endothelial cells in cell culture systems, which suggests possible mechanisms of the genesis of preeclampsia and infertility by the antiphospholipid antibodies. Less

先兆子痫是一种相对常见但神秘的妊娠期疾病，其病因尚未完全阐明。最近，遗传和免疫因素被认为与先兆子痫的发生有关。人的主要组织相容性复合体抗原复合体（major histocompatibility complex antigen complex），包括人白细胞抗原（human leukocyte antigen，HLA），可用于检查包括先兆子痫在内的一些疾病的免疫遗传学基础。因此，我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析子痫前期患者的HLA抗原系统。除了这个分析，我们还调查了HLA抗原系统与不孕症的关联，以及自身抗体，如抗磷脂抗体，在先兆子痫和不孕症的发生中的意义。本研究取得的主要成果如下：1.子痫前期患者HLA-DRB 1 *04和-DRB 1 *0403的频率， ...更多信息 抗心磷脂抗体阴性的子痫前期患者HLA-DRB 1各基因型分布与正常生育妇女无显著性差异，但抗心磷脂抗体阳性的子痫前期患者HLA-DRB 1各基因型分布显著高于正常生育妇女.抗心磷脂抗体阳性不孕症患者HLA-DRB 1 *0403和-DRB 1 *0410的频率明显高于正常生育妇女，HLA-DQB 1 *0501的频率明显低于正常生育妇女。3.原因不明复发性流产患者HLA-DPB 1 *04和-DPB 1 *0402的频率显著高于普通人群.抗心磷脂抗体阳性血清可抑制人脐静脉内皮细胞摄取β-D_（13）-β-D_（1H）-胸苷，提示抗心磷脂抗体可能是子痫前期和不孕症的发病机制之一。少

项目成果

I. Hataya, et al.: "Human leukocyte antigen class II genotype in patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody."Fertil. Steril.. 70. 919-923 (1998)

I. Hataya 等人：“抗心磷脂抗体呈阳性的反复胎儿流产患者的人类白细胞抗原 II 类基因型。”Fertil。

I. Hataya: "Human leukocyte antigen class II genotype in patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody"Fertility and Sterility. 70. 919-923 (1998)

I. Hataya：“抗心磷脂抗体阳性的反复胎儿流产患者的人类白细胞抗原 II 类基因型”生育力和不育。

K. Takakuwa: "Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a polymerase chain reaction-restriction fragment length polymorphism"Human Reproduction. 14. 2980-2986 (19

K. Takakuwa：“使用聚合酶链反应-限制性片段长度多态性对患有严重先兆子痫的日本女性抗心磷脂抗体呈阳性和阴性的 HLA-DRB1 基因型进行研究”人类生殖。

K. Takakuwa: "Possible susceptibility of the HLA-DPB1^*0402 and HLA-DPB1^*04 alleles to unexplained recurrent abortion. Analysis by means of polymerase chain reaction-restricted fragment length polymorphism method"American Journal of Reproductive Immunolo

K. Takakuwa：“HLA-DPB1^*0402 和 HLA-DPB1^*04 等位基因对不明原因复发性流产的可能易感性。通过聚合酶链反应限制片段长度多态性方法进行分析”美国生殖免疫学杂志

K. Takakuwa: "Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a polymerase chain reaction-restriction fragment length polymorphism method"Human Reproduction. 14. 2980-2

K. Takakuwa：“使用聚合酶链反应-限制性片段长度多态性方法研究抗心磷脂抗体阳性和阴性的日本重度子痫前期女性的 HLA-DRB1 基因型”人类生殖。