A functional variant in the 3'-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients

Autor: Lei Jin, Ying Huang, Shengyue Wang, Hui Wu, Yujie Wang, Jing Zhao, Xia Li, Yun Bai, Yingfeng Weng
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
Male
Vascular Endothelial Growth Factor A
Linkage disequilibrium
Heredity
Angiogenesis
Molecular biology
Gene Expression
lcsh:Medicine
Biochemistry
Vascular Medicine
Severity of Illness Index
Linkage Disequilibrium
Brain Ischemia
chemistry.chemical_compound
Habits
0302 clinical medicine
Modified Rankin Scale
Genotype
Medicine and Health Sciences
Smoking Habits
Medicine
lcsh:Science
3' Untranslated Regions
Aged
80 and over
Multidisciplinary
Middle Aged
Prognosis
Enzymes
Vascular endothelial growth factor
Stroke
Nucleic acids
Vascular endothelial growth factor A
Genetic Mapping
Neurology
293T cells
Cell lines
Female
Oxidoreductases
Biological cultures
Luciferase
Research Article
Adult
Risk
medicine.medical_specialty
Cerebrovascular Diseases
Variant Genotypes
DNA construction
Polymorphism
Single Nucleotide
03 medical and health sciences
Internal medicine
Genetics
Humans
Genetic Predisposition to Disease
Non-coding RNA
Alleles
Ischemic Stroke
Aged
Behavior
Binding Sites
Base Sequence
business.industry
lcsh:R
Biology and Life Sciences
Proteins
Odds ratio
Confidence interval
Gene regulation
Research and analysis methods
MicroRNAs
030104 developmental biology
Molecular biology techniques
chemistry
Case-Control Studies
Plasmid Construction
Multivariate Analysis
Enzymology
RNA
lcsh:Q
business
030217 neurology & neurosurgery
Zdroj: PLoS ONE, Vol 12, Iss 2, p e0172709 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: 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 3'UTR 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.
Databáze: OpenAIRE
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