Browsing by Author "Domingues-Montanari, S."
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- Association of a genetic variant in the ALOX5AP with higher risk of ischemic stroke: a case-control, meta-analysis and functional studyPublication . Domingues-Montanari, S.; Fernández-Cadenas, I.; Del Rio-Espinola, A.; Corbeto, N.; Krug, T.; Manso, H.; Gouveia, L.; Sobral, J.; Mendioroz, M.; Fernández-Morales, J.; Alvarez-Sabin, J.; Ribó, M.; Rubiera, M.; Obach, V.; Martí-Fàbregas, J.; Freijo, M.; Serena, J.; Ferro, J.M.; Vicente, A.M.; Oliveira, S.A.; Montaner, J.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.
- TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approachesPublication . 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.; Gaspar, G.; Jiménez-Conde, J.; Rabionet, R.; Ferro, J.M.; Montaner, J.; Vicente, A.M.; Silva, M.R.; Matos, I.; Lopes, G.; Oliveira, S.A.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-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential.