Browsing by Author "Gomes Pires Manso, Helena Isabel"
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- Genetic factors involved in stroke susceptibility and in outcome at three monthsPublication . Gomes Pires Manso, Helena Isabel; Vicente, Asdrid Moura; Silva, Pedro João Neves eStroke is a significant cause of death and disability in developed countries. It is a multifactorial disease, resulting from the interplay between genes and well-known lifestyle/environmental risk factors. Numerous studies have attempted to identify the genetic risk factors predisposing to stroke, but few have investigated the genetic factors involved in stroke outcome. This work aimed at the identification of genes contributing to stroke and influencing patient’s outcome after three months. Four inflammatory genes (IL1B, IL6, MPO and TNF) and two genes involved in the nitric oxide metabolism (NOS1 and NOS3) were tested for association with stroke. The results suggest that the IL6 and MPO influence stroke susceptibility through independent effects and non-additive interactions. Furthermore, they provided novel evidence for the involvement of the NOS1 gene in stroke susceptibility. Several studies have shown the important impact of inflammation, oxidative stress, neurogenesis, angiogenesis and matrix metalloproteinases in stroke-associated brain damage and/or stroke recovery. Association analyses were thus carried out to assess the role of candidate genes involved in inflammatory processes (IL1B, IL6, MPO and TNF) and oxidative stress (NOS1 and NOS3), as well as matrix metalloproteinase genes (MMP2 and MMP9) and growth factor genes (BDNF, FGF2 and VEGFA) in patient’s outcome at three months. MMP2 genetic variants were found associated with patient’s outcome, and the results also indicate that two epistatic interactions between the BDNF and FGF2 genes and between the FGF2 and VEGFA genes influence this phenotype. A genome-wide association study was performed in stroke outcome using DNA pooled samples, to provide novel insights into the mechanisms involved in stroke recovery. The BBS9 and GLIS3 genes were found associated with patient’s outcome at three months. Taken together, these results suggest that stroke susceptibility and outcome are modulated by a combination of main gene effects and gene-gene interactions, independently of stroke risk factors and/or severity parameters, highlighting the complexity of mechanisms predisposing to stroke and influencing recovery afterwards.