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

抗磷脂综合征（APS）的主要临床特征是静脉和动脉血栓形成，反复妊娠丢失和血小板减少，存在抗磷脂抗体，即抗心磷脂抗体（aCL），狼疮抗凝血剂和凝血酶原抗体。在1990年，我们报道了50 kDa的血浆/血清辅助因子β2-糖蛋白I （β2GPI）是aCL与固相CL结合所必需的。通过等电聚焦和免疫印迹鉴定了β2GPI分子的遗传结构变异。最近，β2GPI蛋白多态性的分子基础（密码子为88、247、306和316）及其在美国大量人群、非西班牙裔白人、西班牙裔、黑人和/或日本人中的分布已被报道。β2GPI外显子7多态性导致β2GPI 5结构域247位的缬氨酸-亮氨酸氨基酸在抗β2GPI抗体的磷脂结合位点和表位的隐位之间发生交换。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β2GPI抗原性的形成中起重要作用。

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.