β2-glycoprotein I gene polymorphism ; Risk factor for the development of antiphospholipid syndrome.

β2-糖蛋白I基因多态性；抗磷脂综合征发生的危险因素。

• 批准号: 13470105
• 负责人: KOIKE Takao
• 金额: $ 9.22万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470105/
• 关键词: Antiphospholipid syndrome; Thrombosis; Anticardiolipin antibodies; β2-glycoprotein I; Genetic polymorphism; β2グリコプロテインI; 抗リン脂質抗体症候; リスクファクター

The antiphospholipid syndrome (APS) is defined by predominant clinical features of venous and arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia in the presence of antiphospholipid antibodies, namely anticardiolipin antibodies (aCL), lupus anticoagulant and antiprothrombin antibodies. In 1990, we reported that a 50 kDa plasma/serum cofactor, β2-glycoprotein I (β2GPI), is required for the aCL binding to the solid phase CL.Genetically determined structural variation in the β2GPI molecule has been identified by isoelectric focusing and by immunoblotting. Recently, the molecular basis of β2GPI protein polymorphism (codons at 88, 247, 306, and 316) and its distribution in large U.S. populations, non-Hispanic whites, Hispanics, Blacks and/or Japanese has been reported. β2GPI exon 7 polymorphism leads to a valine-leucine amino acid exchange at position 247 in domain 5 of β2GPI, between the phospholipids binding site and the cryptic site of the epitopes for anti-β2GPI antibodies. The β2GPI polymorphism, valine/leucine^<247>, is correlated with anti-β2GPI antibody production in patients with APS, and valine^<247> may be important in the formation of β2GPI antigenicity.

抗磷脂综合征 (APS) 的主要临床特征是存在抗磷脂抗体（即抗心磷脂抗体 (aCL)、狼疮抗凝物和抗凝血酶原抗体）时出现静脉和动脉血栓、反复妊娠流产和血小板减少。1990 年，我们报道了这一情况。 50 kDa 血浆/血清辅助因子 β2-糖蛋白 I (β2GPI) 是aCL 与固相 CL 结合。最近，通过等电聚焦和免疫印迹鉴定了 β2GPI 分子中基因决定的结构变异（密码子为 88、247、306 和 316）及其分布。据报道，在美国大量人口中，非西班牙裔白人、西班牙裔、黑人和/或日本人存在 β2GPI 外显子 7。多态性导致β2GPI结构域5中的位置247处的缬氨酸-亮氨酸氨基酸交换，位于磷脂结合位点和抗β2GPI抗体表位的隐藏位点之间。β2GPI多态性，缬氨酸/亮氨酸^<247>。与 APS 患者抗 β2GPI 抗体的产生相关，缬氨酸^<247>可能在形成β2GPI 抗原性。

项目成果

小池 隆夫, 他221名: "内科学"朝倉書店. 2297 (2003)

Takao Koike 等 221：《内科》朝仓书店 2297 (2003)。

T., Astumi: "Genetics of antiphopholipid syndrome"Rheumatic disease clinics.. 27:3. 565-572 (2001)

T.，Astumi：“抗磷脂综合征的遗传学”风湿病诊所.. 27:3。

Ieko, M., Nakabayashi, T., Takeda, T., Naitoh, S., Atsumi, T., Koike, T.: "The inhibition of protein C amticoagulamt activity by anti-β2-glycoprotein I(β2GPI)antibodies isolated from patients with antiphospholipid syndrome by chromatography methods"Mod Rh

Ieko, M.、Nakabayashi, T.、Takeda, T.、Naitoh, S.、Atsumi, T.、Koike, T.：“分离的抗 β2-糖蛋白 I(β2GPI) 抗体对蛋白 C 氨凝活性的抑制通过色谱法从抗磷脂综合征患者中提取“Mod Rh

Tsutsumi, A.: "Anti-phosohatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages"AJRI.. 42. 242-244 (2001)

Tsutsumi, A.：“在不明原因的复发性流产患者中并不经常发现抗磷脂酰丝氨酸/凝血酶原抗体”AJRI.. 42. 242-244 (2001)

Matsuura, E., Kobayashi, K., Kasahara, J., Yasuda, T., Makino, H., Koike, T., Shoenfeld, Y.: "Anti-β2-glycoprotein I antibodies and atherosclerosis"Int. Rev. Immunol. 21. 51-66 (2002)

Matsuura, E.、Kobayashi, K.、Kasahara, J.、Yasuda, T.、Makino, H.、Koike, T.、Shoenfeld, Y.：“抗 β2-糖蛋白 I 抗体和动脉粥样硬化”Int。免疫学。 21. 51-66 (2002)