Abstract 4: A Functional Variant in the 3’-utr of Vegf Might Affect Stroke Functional Recovery by Interfering With the Binding Efficiency of Microrna
Background and purpose: While remaining the second most common cause of death worldwide, stroke is also a leading cause of significant disability. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis and neurovascular during stroke functional recovery . Therefore, we hypothesized that variants of the microRNA-binding site in VEGF would affect its expression and functional outcome of stroke. However, the effect of VEGF gene 3'UTR polymorphisms on the prognosis in patients with acute ischemic stroke(IS) in Chinese has not been reported. Methods: The association of VEGF gene 3'UTR variant with IS was investigated in 494 patients and 330 controls. IS was classified into subtypes using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) at the time of admission. Patients were assessed 90 days post-stroke using the Modified Rankin Scale (MRS) to determine stroke outcome. The bioinformatics analysis suggested that the 3′-UTR of VEGF may increase miR regulation of VEGF gene expression, Then we construct luciferase reporter gene vectors containing VEGF gene 3'UTR site and detect microRNA binding stability.Results: The TT genotype resulted in a significant increase in ischemic stroke [OR, 1.679 (95% CI, 1.101-2.554), P 0.015]. But no association between genotypes and TOAST subtypes was shown. The novel finding was that the TT genotype of the VEGF was associated with poor outcome of recovery 3 months after stroke onset [OR, 2.143 (95% CI, 1.108-4.145), P 0.022]. MiR-199a could inhibit the expression of VEGF by directly binding to 3’UTR and C→T may influence the stability of this binding. Conclusions: IS patients with the TT genotype in the 3′-UTR of VEGF might affect stroke functional recovery by interfering with the binding efficiency of microRNA
Author Disclosures: J. Zhao: None. H. Wu: None.
- © 2015 by American Heart Association, Inc.