Evidence for epistatic gene interactions between growth factor genes in stroke outcome

Eur J Neurol. 2012 Aug;19(8):1151-3. doi: 10.1111/j.1468-1331.2011.03625.x. Epub 2012 Jan 10.

Abstract

Background and purpose: Growth factors are thought to modulate neurological function in stroke recovery through effects in angiogenesis, neurogenesis, and neuroprotection.

Methods: We tested the association of variants in the brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) genes, and epistatic interactions between them, with functional outcome in a sample of 546 stroke patients.

Results: While none of the tested genes was independently associated with stroke outcome, two significant gene-gene interaction models were identified. One model combined one BDNF and three FGF2 markers, with a global odds ratio (OR) (95% confidence interval [CI]) of 4.15 [2.86-6.04]. The second model included one FGF2 and two VEGFA markers with a global OR [95% CI] = 2.54 [1.76-3.67].

Conclusions: The results provide evidence for gene interactions in stroke outcome, highlighting the complexity of the recovery mechanisms after a stroke event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics*
  • Epistasis, Genetic / genetics*
  • Fibroblast Growth Factor 2 / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Recovery of Function / genetics*
  • Stroke / genetics*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Brain-Derived Neurotrophic Factor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2