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PDE4D and ALOX5AP genetic variants and risk for Ischemic Cerebrovascular Disease in Sweden.

Abstract：

BACKGROUND:Genetic variants in Phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP) have been shown to confer risk of Ischemic Cerebrovascular Disease (ICVD) in Iceland. We investigated whether these variants associate with ICVD in Sweden. METHODS:Previously published PDE4D and ALOX5AP gene variants were genotyped for cases (685) and controls (751). In PDE4D this consisted of SNP41, SNP45 and microsatellite AC008818-1 and in ALOX5AP four SNPs that define the HapA haplotype. RESULTS:The PDE4D SNPs, showed a non-significant risk in the ICVD group which increased for the Large Artery Atherosclerosis subtype (SNP45: RR=1.43, P=0.063, SNP41: RR=1.57, P=0.018). The SNP haplotype GA (SNP45, SNP41) showed an increased risk for LAA (RR=1.58, P=0.016) and the combined LAA and Cardioembolism (CE) (RR=1.34, P=0.031) subgroups. As the SNPs are in strong LD, this haplotype corresponds to the complement of the protective haplotype in the Icelandic study. No allele of the microsatellite marker, showed association to stroke or any subtype and nor did the Icelandic PDE4D at-risk haplotype (GA0). We did not confirm the association between ALOX5AP HapA haplotype and ICVD, but a non-significant risk was observed in the LAA subtype. CONCLUSION:Our PDE4D findings although non-significant considering the number of markers and phenotypes tested, are consistent with the association observed in the original study, with a trend observed in the whole ICVD group, which was strengthened in the stroke subtype LAA and the combined group of LAA and CE stroke. This supports the notion that PDE4D contributes to the risk of developing stroke.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Kostulas K,Gretarsdottir S,Kostulas V,Manolescu A,Helgadottir A,Thorleifsson G,Gudmundsson LJ,Thorsteinsdottir U,Gulcher JR,Stefansson K,Hillert J

doi

10.1016/j.jns.2007.06.042

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

113-7

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(07)00451-0

journal_volume

263

pub_type

杂志文章

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