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

Manso, H.; Krug, T.; Sobral, J.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Oliveira, S.A.; Vicente, A.M.

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 function...


TTC7B emerges as a novel risk factor for ischemic stroke through the convergenc...

Krug, T.; Gabriel, J.P.; Taipa, R.; Fonseca, B.V.; Domingues-Montanari, S.; Fernandez-Cadenas, I.; Manso, H.; Gouveia, L.O.; Sobral, J.; Albergaria, I.

We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-...


Variants within the nitric oxide synthase 1 gene are associated with stroke sus...

Manso, H.; Krug, T.; Sobral, J.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Oliveira, S.A.; Vicente, A.M.

Animal studies have allowed important insights into the role of the nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3 genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS), influence stroke susceptibility and outcome after a stroke event.


Variants in the inflammatory IL6 and MPO genes modulate stroke susceptibility t...

Vicente, A.M.; Manso, H.; Krug, T.; Sobral, J.; Gaspar, G.; Oliveira, S.; Ferro, J.M.

A complex interplay between genetic background, clinical and life-style factors and the environment is expected to ultimately regulate the onset, acute phase and outcome of stroke. There is substantial evidence that inflammation within the Central Nervous System contributes to stroke risk, and known clinical risk factors for stroke, like atherosclerosis, diabetes, obesity, hypertension, and peripheral infection...


A genome-wide association study using a DNA pooling strategy identifies BBS9 an...

Manso, H.; Paulos-Pinheiro, S.; Krug, T.; Sobral, J.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Oliveira, S.A.; Vicente, A.M.

Stroke is a major cause of morbidity in developed countries and therefore finding adequate treatments to promote patient’s recovery is a priority task, requiring the elucidation of the molecular pathways influencing brain recovery. Few studies, however, have assessed the role of genes in stroke outcome. This study describes a pilot genome-wide association study (GWAS) to identify genetic factors contributing to...


Association of a genetic variant in the ALOX5AP with higher risk of ischemic st...

Domingues-Montanari, S.; Fernández-Cadenas, I.; Del Rio-Espinola, A.; Corbeto, N.; Krug, T.; Manso, H.; Gouveia, L.; Sobral, J.; Mendioroz, M.

Variants in the 5-lipoxygenase-activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) genes have first been associated with ischemic stroke (IS) through whole-genome linkage screens. However, association studies obtained conflicting results. We aimed to investigate the contribution of selected single nucleotide polymorphisms (SNPs) in these genes for the first time in a large Iberian population.


Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase...

Manso, H.; Krug, T.; Sobral, J.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Oliveira, S.A.; Vicente, A.M.

Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis ...


Kalirin: a novel genetic risk factor for ischemic stroke

Krug, T.; Manso, H.; Gouveia, L.; Sobral, J.; Xavier, J.M.; Albergaria, I.; Gaspar, G.; Correia, M.; Viana-Baptista, M.; Simões, R.M.; Pinto, A.N.

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been perfo...


Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese pat...

Rosa, A.; Fonseca, B.V.; Krug, T.; Manso, H.; Gouveia, L.; Albergaria, I.; Gaspar, G.; Correia, M.; Viana-Baptista, M.; Simões, R.M.; Pinto, A.N.

The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the c...


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