Neuroserpin polymorphisms and stroke risk in a biracial population: The stroke prevention in young women study

Veterans Affairs Medical Center, Baltimore, Maryland, USA.
BMC Neurology (Impact Factor: 2.04). 02/2007; 7(1):37. DOI: 10.1186/1471-2377-7-37
Source: PubMed


Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA) on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women.
A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-matched control subjects (43.1% African-American). Neuroserpin single nucleotide polymorphisms (SNPs) chosen through HapMap were genotyped in the study population and assessed for association with stroke.
Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42) of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT) among Caucasians (OR = 2.05, p = 0.023) but not African-Americans (OR = 0.71, p = 0.387). Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only.
This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.

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    • "In animal models of ischemic stroke overexpression of neuroserpin and treatment with neuroserpin led to a decrease in infarct size [5], [8]. Moreover, decreased levels of neuroserpin following stroke correlated with brain damage and polymorphisms in the neuroserpin gene may be associated with the risk of early onset stroke in Caucasian women [9]–[11]. "
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