Gene polymorphisms for plasminogen activator inhibitor-1 tissue plasminogen activator and development of allograft coronary artery disease
Gene polymorphisms for plasminogen activator inhibitor-1 tissue plasminogen activator and development of allograft coronary artery disease
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DOI：
10.1161/01.cir.98.21.2248
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发表时间：
1998-11-24
期刊：
影响因子：
37.8
通讯作者：
Booyse, FM
中科院分区：
文献类型：
--
作者：
Benza, RL;Grenett, HE;Booyse, FM
背景：纤维蛋白溶解活性受损与同种异体移植血管病变（Tx CAD）的存在和严重程度有关。这种损伤可能与某些纤溶蛋白基因多态性的存在有关。方法与结果：为了研究供体特异性纤溶蛋白基因型与冠心病的关系，我们在48例同种异体心脏移植受者中鉴定了供体纤溶酶原激活物抑制剂-1 (PAI-1) HindIII和组织纤溶酶原激活物（TPA） EcoRI限制性片段长度多态性基因型，并将这些基因型与冠心病的发生进行了相关性分析。供体TPA基因型与Tx CAD的存在没有关联。48例患者中，1/1 PAI-1基因型纯合子占17%，2/2 PAI-1基因型占51%，1/2 PAI-1基因型占32%。每种供体PAI-1基因型的受体在12个月和24个月时免于任何CAD的精算自由度分别为1/1 PAI-1基因型的100%和100%，1/2 PAI-1基因型的92%和92%，2/2 PAI-1基因型的75%和45% （P=0.03）。病变的2/2 PAT-1基因型异体移植物受体比不含Tx cad的异体移植物受体缺血时间更长（P=0.02）。结论：这些数据表明，2/2 PAI-1基因型受体发生Tx CAD的风险显著。该基因型可作为预测Tx CAD未来发展的有用筛选工具。
Background-Impaired fibrinolytic activity has been linked to the presence and severity of allograft vasculopathy (Tx CAD). This impairment may be associated with the presence of certain fibrinolytic protein gene polymorphisms.Methods and Results-To investigate the relation between donor-specific fibrinolytic protein genotypes and Tx CAD, we identified donor plasminogen activator inhibitor-1 (PAI-1) HindIII and tissue plasminogen activator (TPA) EcoRI restriction fragment length polymorphisms-based genotypes by Southern blot analysis in 48 recipients of cardiac allografts and correlated these genotypes with the development of CAD. No association was found between donor TPA genotypes and the presence of Tx CAD. Among the 48 patients, 17% were homozygous for the 1/1 PAI-1 genotype, 51% for the 2/2 PAI-1 genotype, and 32% for the 1/2 PAI-1 genotype. The actuarial freedom from any CAD for the recipients with each respective donor PAI-I genotype at 12 and 24 months was 100% and 100% for the 1/1 PAI-1 genotype, 92% and 92% for the 1/2 PAI-1 genotype, and 75% and 45% for the 2/2 PAI-1 genotype (P=0.03). Recipients with a diseased 2/2 PAT-1 genotyped allograft had longer ischemic times (P=0.02) than those recipients with a Tx CAD-free allograft.Conclusions-These data suggest that recipients with a 2/2 PAI-1 genotype are at a significant risk of developing Tx CAD. This genotype may serve as a useful screening tool for predicting the future development of Tx CAD.