4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease
4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease
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DOI：
10.1016/s0140-6736(99)02220-5
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发表时间：
1999-08-14
期刊：
影响因子：
168.9
通讯作者：
Levin, M
中科院分区：
文献类型：
--
作者：
Hermans, PWM;Hibberd, ML;Levin, M
背景：血管内凝血伴皮肤、手指和四肢的梗塞是脑膜炎双球菌败血症的特征。脑膜炎双球菌败血症患儿血浆纤溶酶原激活物抑制物-1(PAI-1)水平高于正常水平。再加上广泛的静脉血栓形成，这一发现表明纤溶功能受损。PAI-1启动子区域存在常见的功能性插入/缺失(4G/5G)多态性。吉恩。我们验证了这一假设，即携带4G/4G基因的儿童会产生更高浓度的PAI-1，发生更严重的凝血障碍，在脑膜炎球菌败血症期间死亡风险更大。方法对175例脑膜炎球菌病患儿(37名来自荷兰鹿特丹，138名来自英国伦敦)和226名对照组(137名来自鹿特丹，89名来自伦敦)进行脑膜炎球菌病预后、PAI-1浓度和ANA PAI-1基因型之间的关系研究。采用酶联免疫吸附试验检测血浆PAI-1浓度，用聚合酶链式反应和杂交法检测PAI-1基因4G/5G多态性，发现入院时PAI-1浓度与临床表现(脓毒症或脑膜炎)及预后相关。死亡儿童的PAI-1浓度中位数显著高于存活儿童(2448[IQR 1115-3191]vs 370[146-914]ng/mL；p
Background Intravascular coagulation with infarction of skin, digits, and limbs is a characteristic feature of meningococcal sepsis. Children with meningococcal sepsis have higher than normal concentrations of plasminogen activator inhibitor 1 (PAI-1) in plasma. Combined with the widespread venous thrombosis, this finding suggests an impairment of fibrinolysis. A common functional insertion/deletion (4G/5G) polymorphism exists in the promoter region of the PAI-1. gene. We tested the hypothesis that children with the 4G/4G genotype produce higher concentrations of PAI-1, develop more severe coagulopathy, and are at greater risk of death during meningococcal sepsis.Methods The relation between meningococcal disease outcome, PAI-1 concentration, ana PAI-1 genotype was investigated in 175 children with meningococcal disease (37 from Rotterdam, the Netherlands, and 138 from London, UK) and 226 controls (137 from Rotterdam, 89 from London). PAI-1 concentrations in plasma were measured by ELISA, and the 4G/5G PAI-1 polymorphism was detected by PCR and hybridisation.Findings Concentrations of PAI-1 on admission correlated with presentation (sepsis or meningitis) and outcome. The median PAI-1 concentration in children who died was substantially higher than that in survivors (2448 [IQR 1115-3191] vs 370 [146-914] ng/mL; p