Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study.
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.
Cole
John W
JW
Veterans Affairs Medical Center, Baltimore, Maryland, USA. jcole@som.umaryland.edu
Naj
Adam C
AC
O'Connell
Jeffrey R
JR
Stine
Oscar C
OC
Sorkin
John D
JD
Wozniak
Marcella A
MA
Stern
Barney J
BJ
Yepes
Manuel
M
Lawrence
Daniel A
DA
Reinhart
Laurie J
LJ
Strickland
Dudley K
DK
Mitchell
Braxton D
BD
Kittner
Steven J
SJ
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
D009479:Neuropeptides; D015843:Serpins; D000097522:Neuroserpin