Evidence for epistatic gene interactions between growth factor genes in stroke outcome.
OBJECTIVE
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.
Departamento Promoção da Saúde e Doenças Crónicas, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
H
H
Manso
T
T
Krug
J
J
Sobral
I
I
Albergaria
G
G
Gaspar
J M
JM
Ferro
S A
SA
Oliveira
A M
AM
Vicente
D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020127:Recovery of Function / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2