Gallek Matthew J, Alexander Sheila A, Crago Elizabeth, Sherwood Paula R, Klamerus Megan, Horowitz Michael B, Poloyac Samuel M, Conley Yvette
College of Nursing, University of Arizona, Tucson, AZ, USA
School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
Biol Res Nurs. 2015 Mar;17(2):185-90. doi: 10.1177/1099800414536261. Epub 2014 May 22.
Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm. Specifically, this study evaluated the differences between variant positive and variant negative groups of nine different ET-1 single-nucleotide polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One functional SNP and eight ET-1 tagging SNPs were selected because they represent genetic variability in the entire ET-1 gene. The variant negative group of SNP rs2070699 was associated with a significantly higher ET-1 exposure rate than the variant positive group (p = 0.004), while the variant positive group of the rs5370 group showed a trend toward association with a higher ET-1 exposure rate (p = 0.051). Other SNPs were not informative. This is the first study to show differences in ET-1 exposure rate 72 hr before angiography in relation to ET-1 genotypes. These exploratory findings need to be replicated in a larger study; if replicated, these differences in genotypes may be a way to inform clinicians of those patients at a higher risk of increased ET-1 protein levels, which may lead to a higher risk of angiographic vasospasm.
动脉瘤性蛛网膜下腔出血是一种发病率和死亡率都很高的中风类型。内皮素-1（ET-1）水平升高与脑血管痉挛风险增加有关，而脑血管痉挛又与发病率增加相关。本研究的目的是调查在脑血管痉挛高风险受试者中，血管造影血管痉挛测量前72小时测量的脑脊液（CSF）中ET-1基因型与ET-1蛋白水平之间的关系。具体而言，本研究评估了9种不同的ET-1单核苷酸多态性（SNP）的变异阳性组和变异阴性组在ET-1蛋白暴露率方面的差异。使用酶联免疫吸附测定法定量CSF中的ET-1蛋白水平。选择了一个功能性SNP和八个ET-1标签SNP，因为它们代表了整个ET-1基因的遗传变异性。SNP rs2070699的变异阴性组的ET-1暴露率显著高于变异阳性组（p = 0.004），而rs5370组的变异阳性组显示出与较高的ET-1暴露率相关的趋势（p = 0.051）。其他SNP无信息价值。这是第一项显示血管造影前72小时ET-1暴露率与ET-1基因型相关差异的研究。这些探索性发现需要在更大规模的研究中进行重复验证；如果得到重复验证，这些基因型差异可能是一种告知临床医生哪些患者ET-1蛋白水平升高风险更高的方法，而这可能导致血管造影血管痉挛风险更高。
