Research article

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

John W Cole^1,2 , Adam C Naj³ , Jeffrey R O'Connell^4,5 , Oscar C Stine^4,5 , John D Sorkin¹ , Marcella A Wozniak^1,2 , Barney J Stern^1,2 , Manuel Yepes⁶ , Daniel A Lawrence⁷ , Laurie J Reinhart⁵ , Dudley K Strickland⁸ , Braxton D Mitchell^4,5 and Steven J Kittner^1,2

¹Veterans Affairs Medical Center, Baltimore, Maryland, USA

²Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA

³Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

⁴Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

⁵Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

⁶Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA

⁷Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

⁸Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA

author email corresponding author email

BMC Neurology 2007, 7:37doi:10.1186/1471-2377-7-37

Published:	25 October 2007

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.