The Thrombospondin-1 N700s Polymorphism is Associated with Early Myocardial Infarction Without Altering Von Willebrand Factor Multimer Size.
From: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jzwicker@bidmc.harvard.edu
Blood
- Publish Date: Aug 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 4
- Pages: 1280-3
- Medium: Print
- Language: English
- Citation (JAMA): Zwicker Jeffrey I, Peyvandi Flora, Palla Roberta, et al. The Thrombospondin-1 N700s Polymorphism is Associated with Early Myocardial Infarction Without Altering Von Willebrand Factor Multimer Size.. Blood Aug 2006;108:1280-3
Abstract
The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.
Mesh Headings (Keywords): Alleles, Case-Control Studies, Disease-Free Survival, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Myocardial Infarction, Polymorphism, Single Nucleotide, Protein Binding, Protein Structure, Tertiary, Risk Factors, Thrombospondin 1, von Willebrand Factor
Check for Full Text / PubMed Unique Identifier (PMID): 16684956
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