Association of variants in the vascular endothelial growth factor receptor 2 gene and the risk of hemorrhagic stroke

Abstract

Objective: To assess whether variants in the vascular endothelial growth actor receptor 2 (VEGFR-2) gene confer susceptibility to stroke risk. Methods: Association between gene variant rs2305948 (Val297Ile) and the risk of stroke was investigated in a multi-center case-control study, which comprised of 1849 patients with stroke (812 cerebral atherothrombosis, 530 lacunar infarction, and 507 intracerebral hemorrhage) and 1798 controls, and then replicated in the second independent stroke study (327 cases and 327 controls). The effect of Val297Ile on the binding ability of VEGFR-2 to VEGF was determined by a radioligand binding assay. Results: The frequencies of carriers with variant 297Ile were significantly higher in patients with hemorrhagic stroke than in controls [297Val/Ile: 155(30.6%) versus 351 (19.5%), 297Ile/Ile: 18(3.2%) versus 16(1.0%); P < 0.01]. The variant 297 lie was significantly associated with increased risk of hemorrhagic stroke (odds ratio 2.25, 95% confidence interval 1.70-2.96; P < 0.01), and replication in the second stroke study obtained similar results. The substitution of Val to He at the amino acid residue 297 led to an increased equilibrium dissolved constant between VEGF and its receptor VEGFR-2 [297Val (87 ± 9) pmol/L versus 297Ile (195 ± 36) pmol/L, P < 0.01]. Conclusions: The VEGFR-2 gene variants may serve as novel genetic markers for the risk of hemorrhagic stroke. Copyright © 2011 by the Chinese Medical Association.