Angiotensin converting enzyme insertion /deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome
Angiotensin converting enzyme insertion /deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome
复制标题
DOI：
10.1164/rccm.2108086
复制
发表时间：
2002-09-01
影响因子：
24.7
通讯作者：
Laurent, GJ
中科院分区：
文献类型：
--
作者：
Marshall, RP;Webb, S;Laurent, GJ
急性呼吸窘迫综合征(ARDS)是一种通常是致命的疾病，其遗传易感性被认为是一种疾病，尽管到目前为止还没有发现特定的基因。血管紧张素转换酶(ACE)通过影响肺血管张力/通透性、上皮细胞存活和成纤维细胞活化，在ARDS的发病机制中发挥潜在作用。血浆ACE活性变异的47%是由ACE插入/缺失(I/D)多态引起的，D等位基因与较高的活性相关。因此，我们假设D等位基因的存在与ARDS的发生有关。符合美国/欧洲ARDS共识委员会标准的96名白人患者与来自三个对照组的个人一起进行了ACE基因分型：88名非ARDS呼吸衰竭患者在重症监护病房(ICU)进行呼吸机治疗，174名ICU患者接受冠状动脉旁路移植术，以及来自普通人群组的1906人。与重症监护病房(p=0.00008)、冠状动脉旁路移植术(p=0.0009)和普通人群对照组(p=0.00004)相比，急性呼吸窘迫综合征患者的DD基因频率增加，且与死亡率显著相关(p<；0.02)。这些数据表明肾素-血管紧张素系统在ARDS的发病机制中具有潜在的作用，并首次将遗传因素与ARDS的发生和发展联系在一起。
Acute respiratory distress syndrome (ARDS) is an often fatal condition for which a genetic predisposition is postulated, although no specific genes have been identified to date. Angiotensin converting enzyme (ACE) has a potential role in the pathogenesis of ARDS via effects on pulmonary vascular tone/permeability, epithelial cell survival, and fibroblast activation. Forty-seven percent of the variance in plasma ACE activity is accounted for by the ACE insertion/deletion (I/D) polymorphism, the D allele being associated with higher activity. We therefore hypothesized that the presence of the D allele would be associated with the development of ARDS. Ninety-six white patients fulfilling American/European Consensus Committee criteria for ARDS were genotyped for the ACE polymorphism together with individuals from three comparison groups: 88 white patients with non-ARDS respiratory failure ventilated in the intensive care unit (ICU), 174 ICU patients undergoing coronary artery bypass grafting, and 1,906 individuals from a general population group. DD genotype frequency was increased in the patients with ARDS compared with the ICU (p = 0.00008), coronary artery bypass grafting (p = 0.0009), and general population group (p = 0.00004) control groups and was significantly associated with mortality in the ARDS group (p < 0.02). These data suggest a potential role for renin-angiotensin systems in the pathogenesis of ARDS and for the first time implicate genetic factors in the development and progression of this syndrome.