Endler Georg, Mannhalter Christine, Sunder-Plassmann Heike, Schillinger Martin, Klimesch Alexandra, Exner Markus, Kapiotis Sonja, Meier Susanne, Kunz Freja, Raiger Elisabeth, Huber Kurt, Wagner Oswald, Sunder-Plassmann Raute
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Division of Molecular Biology, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
J Mol Med (Berl). 2002 Dec;80(12):791-5. doi: 10.1007/s00109-002-0385-8. Epub 2002 Nov 13.
Elevated plasma cell membrane glycoprotein 1 (PC-1) expression and the frequent PC-1 K121Q polymorphism have recently been associated with insulin resistance. Since insulin resistance represents an important risk factor for atherosclerotic vascular disease and myocardial infarction, we investigated the involvement of the PC-1 K121Q polymorphism in the development of myocardial infarction. We analyzed two independent series of cardiovascular patients at a defined end-point of atherosclerotic vascular disease (those having suffered myocardial infarction) for the PC-1 K121Q mutation by a newly developed mutagenic separated PCR assay. In both patient groups the presence of the Q allele was significantly associated with younger age at the time of first myocardial infarction, suggesting a more rapid progression of endothelial dysfunction. In a multivariate analysis carriers of the 121Q allele from Vienna and from Central Germany exhibited a 2.6- and a 4.2-increased odds, respectively, for suffering myocardial infarction within the first tertile of age (<51 and <48 years, respectively). Our data indicate that the PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction.
血浆细胞膜糖蛋白1(PC-1)表达升高以及常见的PC-1 K121Q多态性最近被认为与胰岛素抵抗有关。由于胰岛素抵抗是动脉粥样硬化性血管疾病和心肌梗死的重要危险因素,我们研究了PC-1 K121Q多态性在心肌梗死发生中的作用。我们通过新开发的诱变分离PCR分析法,分析了两组独立的心血管疾病患者(患有心肌梗死的患者)在动脉粥样硬化性血管疾病的特定终点时的PC-1 K121Q突变情况。在两组患者中,Q等位基因的存在与首次心肌梗死时的年龄较轻显著相关,提示内皮功能障碍进展更快。在多变量分析中,来自维也纳和德国中部的121Q等位基因携带者在年龄的第一个三分位数内(分别为<51岁和<48岁)发生心肌梗死的几率分别增加了2.6倍和4.2倍。我们的数据表明,PC-1 121Q等位基因可能独立于其他已确定的早期心肌梗死危险因素而使人易患该病。检测PC-1 K121Q多态性对于有动脉粥样硬化性血管疾病和心肌梗死家族史的患者可能有价值。