A functional variant in the 3'-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients.
A functional variant in the 3'-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients.
复制标题
VEGF 3'-UTR 的功能变异可预测中国患者缺血性中风的 90 天结果
DOI：
10.1371/journal.pone.0172709
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Zhao J;Bai Y;Jin L;Weng Y;Wang Y;Wu H;Li X;Huang Y;Wang S
血管内皮生长因子（VEGF）在血管生成和血管生成中起着关键作用，与卒中后功能恢复相关。然而，VEGFA基因多态性对缺血性卒中（IS）预后的影响却鲜有报道。因此，我们通过建立logistic多元回归模型，研究了中国人群中494例IS患者和337名健康对照者的+936C/T变异（rs3025039）与易感性和90天预后的关系。分别根据美国国立卫生研究院中风量表和改良的兰金量表评估入院时的中风严重程度和90天的结局。rs3025039基因型与肺癌的易感性（P = 0.229）和严重程度（P = 0.734）均无显著相关性。然而，当我们将308例IS患者根据不同的结局分为两组时，我们发现rs3025039 TC+TT基因型显著增加了恢复不良的风险[校正比值比（OR），1.99; 95%置信区间（CI），1.18-3.37]。有趣的是，我们观察到另一个3个UTR变体，+1451C/T（rs3025040），与+936C/T表现出强烈的连锁不平衡（r2 = 1.0），并且位于预测的microRNA结合位点。rs3025040 T等位基因显著降低了四种细胞系中的荧光素酶活性，这表明miRNA-mRNA相互作用的潜在破坏将导致VEGF表达水平降低。我们的数据表明，+936 C/T变异通过影响miR-199 a和miR-199 b与VEGF mRNA在rs30250340多态性位点的结合，显著增加了卒中预后不良的风险。
Vascular endothelial growth factor (VEGF) plays critical roles in angiogenesis and vasculogenesis, which are associated with post-stroke functional recovery. However, the effects of the VEGFA polymorphisms on the outcome of ischemic stroke (IS) have been rarely reported. We therefore investigated the associations of +936C/T variant (rs3025039) with the susceptibilities and the 90-day outcomes from 494 IS patients and 337 healthy controls in Chinese population through the establishment of logistic multivariate regression model. Stroke severity at admission and outcome of 90 days were respectively assessed according to the National Institutes of Health Stroke Scale and the modified Rankin Scale. The analysis showed that there were no significant associations of the rs3025039 genotypes with the susceptibility (P = 0.229) and the severity (P = 0.734). However, when we divided the 308 IS patients into two groups according to the different outcomes, we found that the rs3025039 TC+TT genotype significantly increased the risk of poor recovery [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI), 1.18–3.37]. Interestingly, we observed another 3ˈUTR variant, +1451C/T (rs3025040), exhibited strong linkage disequilibrium (r2 = 1.0) with +936C/T and was located in a predicted microRNA-binding site. The rs3025040 T allele significantly decreased the luciferase activities in four cell lines, which indicated a potential disruption of the miRNA-mRNA interaction that would result in lower VEGF expression levels. Our data suggested that the +936C/T variants significantly increased the risk of poorer stroke outcome by affecting the bindings of miR-199a and miR-199b to VEGF mRNA at the rs30250340 polymorphic site.