title: Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study.
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.
  
  
  CONCLUSIONS
  This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.
authors.affiliation: Veterans Affairs Medical Center, Baltimore, Maryland, USA. jcole@som.umaryland.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.forename: Adam C
authors.initials: AC
authors.lastname: Naj
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Stine
authors.forename: John D
authors.initials: JD
authors.lastname: Sorkin
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Stern
authors.forename: Manuel
authors.initials: M
authors.lastname: Yepes
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lawrence
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Reinhart
authors.forename: Dudley K
authors.initials: DK
authors.lastname: Strickland
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People; D016022:Case-Control Studies; D018672:Community Health Planning; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D015843:Serpins / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*; D044465:White People; D000097522:Neuroserpin; D001741:Black or African American
chemical_list: D009479:Neuropeptides; D015843:Serpins; D000097522:Neuroserpin