In:
Cerebrovascular Diseases, S. Karger AG, Vol. 29, No. 6 ( 2010), p. 528-537
Abstract:
〈 i 〉 Background: 〈 /i 〉 Variants in the 5-lipoxygenase-activating protein 〈 i 〉 (ALOX5AP) 〈 /i 〉 and phosphodiesterase 4D 〈 i 〉 (PDE4D) 〈 /i 〉 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. 〈 i 〉 Methods: 〈 /i 〉 A case-control design was used to analyze one SNP in 〈 i 〉 ALOX5AP 〈 /i 〉 and five SNPs in 〈 i 〉 PDE4D 〈 /i 〉 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, 〈 i 〉 ALOX5AP 〈 /i 〉 gene expression levels were determined in controls and IS cases. 〈 i 〉 Results: 〈 /i 〉 A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in 〈 i 〉 ALOX5AP 〈 /i 〉 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] . 〈 i 〉 ALOX5AP 〈 /i 〉 gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of 〈 i 〉 ALOX5AP 〈 /i 〉 (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 〈 i 〉 PDE4D 〈 /i 〉 with IS was observed in our study. 〈 i 〉 Conclusions: 〈 /i 〉 The 〈 i 〉 ALOX5AP 〈 /i 〉 SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with 〈 i 〉 ALOX5A 〈 /i 〉 P expression levels. The role of this gene in stroke merits further investigation.
Type of Medium:
Online Resource
ISSN:
1015-9770
,
1421-9786
Language:
English
Publisher:
S. Karger AG
Publication Date:
2010
detail.hit.zdb_id:
1482069-9
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