Ladenvall Per, Johansson Lars, Jansson Jan-Håkan, Jern Sverker, Nilsson Torbjörn K, Tjärnlund Anna, Jern Christina, Boman Kurt
Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
Thromb Haemost. 2002 Jan;87(1):105-9.
We recently identified a polymorphic Sp1 binding site in an enhancer at the tissue-type plasminogen activator (tPA) locus (tPA -7,351C/T), which was associated with vascular tPA release. Subjects homozygous for the -7,351C allele had twice the tPA release rate compared to subjects carrying the -7,351T allele. In this study we tested the hypothesis that the tPA -7,351C/T polymorphism is associated with myocardial infarction (MI). In a population-based prospective nested case-control study within northern Sweden, genotypes were determined among 61 MI cases and 120 controls. In a multivariate model, the tPA -7,351C/T polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31-5.50), tPA antigen (OR 1.16; 95% CI 1.07-1.25) and apo A-I (OR, 0.997; 95% CI 0.995-0.999) were independently associated with a first MI. These findings suggest that genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information.
我们最近在组织型纤溶酶原激活剂（tPA）基因座的一个增强子中鉴定出一个多态性Sp1结合位点（tPA -7,351C/T），它与血管tPA释放有关。与携带-7,351T等位基因的受试者相比，-7,351C等位基因纯合的受试者tPA释放率高出两倍。在本研究中，我们检验了tPA -7,351C/T多态性与心肌梗死（MI）相关的假设。在瑞典北部一项基于人群的前瞻性巢式病例对照研究中，确定了61例MI患者和120例对照的基因型。在多变量模型中，tPA -7,351C/T多态性（T等位基因携带者的OR为2.68；95%CI为1.31 - 5.50）、tPA抗原（OR为1.16；95%CI为1.07 - 1.25）和载脂蛋白A-I（OR为0.997；95%CI为0.995 - 0.999）与首次MI独立相关。这些发现表明，局部tPA释放和循环稳态tPA水平的遗传标记携带独立的预后信息。
