BACKGROUND: 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. METHODS: A case-control design was used to analyze one SNP in ALOX5AP and five SNPs in PDE4D in a total of 1,092 IS patients and 781 healthy controls of two different subsets from Spain and Portugal. The analysis was adjusted for confounding variables and the results were integrated in a meta-analysis of all case-control studies. In addition, ALOX5AP gene expression levels were determined in controls and IS cases. RESULTS: A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in ALOX5AP was a risk factor for IS after Bonferroni correction [OR = 1.22 (1.06-1.40); p = 0.006]. A second meta-analysis of white populations confirmed these results [OR = 1.18 (1.07-1.31); p = 0.001]. ALOX5AP gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of ALOX5AP (p = 0.001) and mRNA levels were higher in IS cases (2.8 +/- 2.4%) than in controls (1.4 +/- 1.3%; p = 0.003). No association of the variants in PDE4D with IS was observed in our study. CONCLUSIONS: The ALOX5AP SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with ALOX5AP expression levels. The role of this gene in stroke merits further investigation. Copyright 2010 S. Karger AG, Basel.
BACKGROUND: 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. METHODS: A case-control design was used to analyze one SNP in ALOX5AP and five SNPs in PDE4D in a total of 1,092 IS patients and 781 healthy controls of two different subsets from Spain and Portugal. The analysis was adjusted for confounding variables and the results were integrated in a meta-analysis of all case-control studies. In addition, ALOX5AP gene expression levels were determined in controls and IS cases. RESULTS: A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in ALOX5AP was a risk factor for IS after Bonferroni correction [OR = 1.22 (1.06-1.40); p = 0.006]. A second meta-analysis of white populations confirmed these results [OR = 1.18 (1.07-1.31); p = 0.001]. ALOX5AP gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of ALOX5AP (p = 0.001) and mRNA levels were higher in IS cases (2.8 +/- 2.4%) than in controls (1.4 +/- 1.3%; p = 0.003). No association of the variants in PDE4D with IS was observed in our study. CONCLUSIONS: The ALOX5AP SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with ALOX5AP expression levels. The role of this gene in stroke merits further investigation. Copyright 2010 S. Karger AG, Basel.
Authors: Tiago Krug; João Paulo Gabriel; Ricardo Taipa; Benedita V Fonseca; Sophie Domingues-Montanari; Israel Fernandez-Cadenas; Helena Manso; Liliana O Gouveia; João Sobral; Isabel Albergaria; Gisela Gaspar; Jordi Jiménez-Conde; Raquel Rabionet; José M Ferro; Joan Montaner; Astrid M Vicente; Mário Rui Silva; Ilda Matos; Gabriela Lopes; Sofia A Oliveira Journal: J Cereb Blood Flow Metab Date: 2012-03-28 Impact factor: 6.200
Authors: Håkan Lövkvist; Sandra Olsson; Peter Höglund; Olle Melander; Christina Jern; Marketa Sjögren; Gunnar Engström; J Gustav Smith; Bo Hedblad; Gunnar Andsberg; Hossein Delavaran; Katarina Jood; Ulf Kristoffersson; Holger Luthman; Bo Norrving; Arne Lindgren Journal: Eur J Hum Genet Date: 2012-01-25 Impact factor: 4.246
Authors: Mahmoud Merhi; Sally Demirdjian; Essa Hariri; Nada Sabbah; Sonia Youhanna; Michella Ghassibe-Sabbagh; Joseph Naoum; Marc Haber; Raed Othman; Samer Kibbani; Elie Chammas; Roy Kanbar; Hamid El Bayeh; Youssef Chami; Antoine Abchee; Daniel E Platt; Pierre Zalloua; Georges Khazen Journal: Inflamm Res Date: 2015-04-24 Impact factor: 4.575