The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size

Jeffrey I. Zwicker, Flora Peyvandi, Roberta Palla, Rossana Lombardi, Maria Teresa Canciani, Andrea Cairo, Diego Ardissino, Luisa Bernardinelli, Kenneth A. Bauer, Jack Lawler, Pier Mannucci

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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 vonWillebrand 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.

Original languageEnglish
Pages (from-to)1280-1283
Number of pages4
JournalBlood
Volume108
Issue number4
DOIs
Publication statusPublished - Aug 15 2006

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Thrombospondin 1
von Willebrand Factor
Polymorphism
Myocardial Infarction
Alleles
Odds Ratio
Confidence Intervals
Platelets
Case-Control Studies
Blood Platelets
Calcium
Phenotype

ASJC Scopus subject areas

  • Hematology

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The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size. / Zwicker, Jeffrey I.; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A.; Lawler, Jack; Mannucci, Pier.

In: Blood, Vol. 108, No. 4, 15.08.2006, p. 1280-1283.

Research output: Contribution to journalArticle

Zwicker, Jeffrey I. ; Peyvandi, Flora ; Palla, Roberta ; Lombardi, Rossana ; Canciani, Maria Teresa ; Cairo, Andrea ; Ardissino, Diego ; Bernardinelli, Luisa ; Bauer, Kenneth A. ; Lawler, Jack ; Mannucci, Pier. / The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size. In: Blood. 2006 ; Vol. 108, No. 4. pp. 1280-1283.
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