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

• Type of Material: Article
• Authors: John W Cole, Veterans Affairs Medical Center; Adam C Naj, Johns Hopkins University; Jeffrey R O'Connell, University of Maryland School of Medicine; Oscar C Stine, University of Maryland School of Medicine; John D Sorkin, Veterans Affairs Medical Center; Marcella A Wozniak, Veterans Affairs Medical Center; Barney J Stern, Veterans Affairs Medical Center; Manuel Yepes, Emory University; Daniel A Lawrence, University of Michigan Medical School; Laurie J Reinhart, University of Maryland School of Medicine; Dudley K Strickland, University of Maryland School of Medicine; Braxton D Mitchell, University of Maryland School of Medicine; Steven J Kittner, Veterans Affairs Medical Center
• Language: English
• Date: 2007
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2007 Cole et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biomedcentral.com/1471-2377/7/37
• Title of Journal or Parent Work: BMC Neurology
• ISSN: 1471-2377
• Volume: 7
• Issue: 37
• Grant/Funding Information: Dr. Cole's efforts on this project were supported in part by the Department of Veterans Affairs, Baltimore, Office of Research and Development, Medical Research Service; the Department of Veterans Affairs Stroke Research Enhancement Award Program; the University of Maryland General Clinical Research Center (Grant M01 RR 165001), General Clinical Research Centers Program, National Center for Research Resources, NIH, and; an American Heart Association Beginning Grant-in-Aid (Grant 0665352U).; Dr. Kittner was supported in part by the Department of Veterans Affairs, Baltimore, Office of Research and Development, Medical Research Service, and Geriatrics Research, Education and Clinical Center, and Stroke Research Enhancement Award Program; a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention; the National Institute of Neurological Disorders and Stroke and the NIH Office of Research on Women's Health; the National Institute on Aging Pepper Center (Grant P60 12583); and the University of Maryland General Clinical Research Center (Grant M01 RR 165001), General Clinical Research Centers Program, National Center for Research Resources, NIH.; Dr. Sorkin was supported by the Baltimore VA Medical Center, Office of Research and Development, Medical Research Service, and Geriatrics Research, Education, and Clinical Center; the University of Maryland Claude D. Pepper Older Americans Independence Center; the Clinical Nutrition Research Unit of the University of Maryland, and; the Baltimore VA Medical Center, Center for Excellence in Robotics.
• Research Categories: Health Sciences, Health Care Management; Health Sciences, General; Health Sciences, Rehabilitation and Therapy

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.