Literature DB >> 16100023

Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with ischemic stroke susceptibility in young black women.

Timothy D Howard1, Wayne H Giles, Jianfeng Xu, Marcella A Wozniak, Ann M Malarcher, Leslie A Lange, Richard F Macko, Monica J Basehore, Deborah A Meyers, John W Cole, Steven J Kittner.   

Abstract

BACKGROUND AND
PURPOSE: Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility.
METHODS: We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4.
RESULTS: Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective.
CONCLUSIONS: Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.

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Year:  2005        PMID: 16100023      PMCID: PMC1494105          DOI: 10.1161/01.STR.0000177978.97428.53

Source DB:  PubMed          Journal:  Stroke        ISSN: 0039-2499            Impact factor:   7.914


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