Crainich P, Jenny N S, Tang Z, Arnold A M, Kuller L H, Manolio T, Sharrett A R, Tracy R P
Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont 05446, USA.
J Thromb Haemost. 2003 Aug;1(8):1799-804. doi: 10.1046/j.1538-7836.2003.00255.x.
Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.
循环中的纤溶酶原激活物抑制剂-1(PAI-1)水平升高可能会增加心血管疾病(CVD)的风险。PAI-1启动子4G/5G多态性的4G等位基因与PAI-1水平升高有关。我们在心血管健康研究(CHS)的老年参与者中研究了PAI-1 4G/5G基因型与CVD事件之间的关联。我们在CHS的一项巢式病例对照研究中测量了4G/5G基因型。病例包括新发心绞痛、心肌梗死(MI)和中风。在选定的老年队列中,未发现4G/5G基因型与纤维蛋白溶解标志物或CVD风险相关。病例对照状态的基因型频率无差异(5G/5G频率为16%-22%;卡方检验P=0.07)。当将至少有一个5G等位基因的个体与4G/4G纯合子进行比较时,5G等位基因与新发CVD事件无关。当将4G/4G和4G/5G基因型的个体与5G/5G纯合子进行比较时,至少有一个4G等位基因的存在同样与新发CVD无关。我们的结果表明,PAI-1 4G/5G启动子多态性与老年人的CVD危险因素或新发CVD事件无关。