title: [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 297Ile 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 Ile 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.
authors: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education, Sino-German Laboratory for Molecular Medicine, Fu Wai Hospital and Cardiovascular Institute, Beijing 100037, China.
authors: Wei-Li
authors: WL
authors: Zhang
authors: Kai
authors: K
authors: Sun
authors: Yi-Bo
authors: YB
authors: Wang
authors: Yi
authors: Y
authors: Zheng
authors: Lu-Hong
authors: LH
authors: Wan
authors: Qin
authors: Q
authors: Qin
authors: Dao-Wen
authors: DW
authors: Wang
authors: Yu-Hua
authors: YH
authors: Liao
authors: Ai-Qun
authors: AQ
authors: Ma
authors: Zhi-Ming
authors: ZM
authors: Zhu
authors: Ru-Tai
authors: RT
authors: Hui
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000235:genetics*; D004730:Endothelium, Vascular; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames; D012307:Risk Factors; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2