GENETIC-VARIATION AT THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 LOCUS IS ASSOCIATED WITH ALTERED LEVELS OF PLASMA PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY
GENETIC-VARIATION AT THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 LOCUS IS ASSOCIATED WITH ALTERED LEVELS OF PLASMA PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY
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DOI：
10.1161/01.atv.11.1.183
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发表时间：
1991-01-01
期刊：
影响因子：
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通讯作者：
HUMPHRIES, S
中科院分区：
文献类型：
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作者：
DAWSON, S;HAMSTEN, A;HUMPHRIES, S
纤溶酶原激活剂抑制剂-1（PAI-1）是组织型纤溶酶原激活剂的快速抑制剂，已被证明是年轻时复发性心肌梗死（MI）的独立危险因素。 为了研究 PAI-1 基因的遗传变异是否影响血浆 PAI-1 水平，我们对 145 名 45 岁之前患有 MI 的患者样本以及 95 名年龄相近的健康个体样本进行了 PAI-1 基因座两个多态性的基因分型。 对所有个体的血浆 PAI-1 水平以及其他纤溶和代谢风险指标进行了测量。 本研究中使用了 HindIII 限制性片段长度多态性 (RFLP) 以及之前未报道的 PAI-1 基因座上的八等位基因二核苷酸重复多态性。 二核苷酸重复多态性和HindIII RFLP存在强连锁不平衡。 患者组和对照组之间任一多态性的等位基因频率没有差异。 然而，较小的二核苷酸重复等位基因与患者样本中较高的血浆 PAI-1 水平显着相关 (p = 0.03)。 这种关联在对照样本中也很明显，但不是显着水平。 甘油三酯对血浆 PAI-1 水平影响的回归系数差异表明，甘油三酯对 PAI-1 的调节具有基因型特异性。 我们的数据表明，该位点的遗传变异导致血浆 PAI-1 水平的个体间差异，这对于纤维蛋白溶解和 MI 的发病机制很重要。
Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of tissue-type plasminogen activator, has been shown to be an independent risk factor for recurrent myocardial infarction (MI) at a young age. To investigate whether genetic variation in the PAI-1 gene is affecting plasma PAI-1 levels, a sample of 145 patients with an MI before the age of 45 years was genotyped for two polymorphisms at the PAI-1 locus, together with a sample of 95 healthy individuals of a similar age. All individuals were measured for plasma PAI-1 levels as well as for other fibrinolytic and metabolic risk indicators. A HindIII restriction fragment length polymorphism (RFLP) was used in this study in conjunction with a previously unreported eight-allele dinucleotide repeat polymorphism at the PAI-1 locus. The dinucleotide repeat polymorphism and HindIII RFLP were in strong linkage disequilibrium. There was no difference in the frequency of alleles of either polymorphism between patient and control groups. However, the smaller dinucleotide repeat alleles were significantly associated (p = 0.03) with higher plasma PAI-1 levels in the patient sample. This association was also apparent in the control sample but not a significant levels. Differences in regression coefficients for the effect of triglycerides on plasma PAI-1 levels suggest that triglyceride regulation of PAI-1 is genotype specific. Our data suggest that genetic variation at this locus contributes to between-individual differences in the level of plasma PAI-1, which is important in fibrinolysis and the pathogenesis of MI.