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

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.