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

Cole JW, Naj AC, O'Connell JR, Stine OC, Sorkin JD, Wozniak MA, Stern BJ, Yepes M, Lawrence DA, Reinhart LJ, Strickland DK, Mitchell BD, Kittner SJ - BMC Neurol (2007)

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterans Affairs Medical Center, Baltimore, Maryland, USA. jcole@som.umaryland.edu

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.

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Related in: MedlinePlus

Haplotype block structure among Caucasians and African-Americans.
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Figure 2: Haplotype block structure among Caucasians and African-Americans.

Mentions: Figure 2 shows the LD pattern observed among African-Americans and Caucasians. Within both race groups, a haplotype block including SNPs rs6797312 and rs6775296 was observed. Additionally, relatively strong linkage disequilibrium was seen among Caucasians between SNPs rs6797312 and rs2420034. Based upon these observations, we chose to perform race-specific haplotype analyses among Caucasians to include two two-SNP haplotype blocks including rs6797312–rs6775296 and rs24240034–rs6797312, and the three SNP haplotype block rs24240034–rs6797312–rs6775296. Among African-Americans, the two-SNP haplotype block rs6797312–rs6775296 was evaluated.


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

Cole JW, Naj AC, O'Connell JR, Stine OC, Sorkin JD, Wozniak MA, Stern BJ, Yepes M, Lawrence DA, Reinhart LJ, Strickland DK, Mitchell BD, Kittner SJ - BMC Neurol (2007)

Haplotype block structure among Caucasians and African-Americans.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2169251&req=5

Figure 2: Haplotype block structure among Caucasians and African-Americans.
Mentions: Figure 2 shows the LD pattern observed among African-Americans and Caucasians. Within both race groups, a haplotype block including SNPs rs6797312 and rs6775296 was observed. Additionally, relatively strong linkage disequilibrium was seen among Caucasians between SNPs rs6797312 and rs2420034. Based upon these observations, we chose to perform race-specific haplotype analyses among Caucasians to include two two-SNP haplotype blocks including rs6797312–rs6775296 and rs24240034–rs6797312, and the three SNP haplotype block rs24240034–rs6797312–rs6775296. Among African-Americans, the two-SNP haplotype block rs6797312–rs6775296 was evaluated.

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterans Affairs Medical Center, Baltimore, Maryland, USA. jcole@som.umaryland.edu

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.

Show MeSH
Related in: MedlinePlus