title: The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.
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.
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jzwicker@bidmc.harvard.edu
authors: Jeffrey I
authors: JI
authors: Zwicker
authors: Flora
authors: F
authors: Peyvandi
authors: Roberta
authors: R
authors: Palla
authors: Rossana
authors: R
authors: Lombardi
authors: Maria Teresa
authors: MT
authors: Canciani
authors: Andrea
authors: A
authors: Cairo
authors: Diego
authors: D
authors: Ardissino
authors: Luisa
authors: L
authors: Bernardinelli
authors: Kenneth A
authors: KA
authors: Bauer
authors: Jack
authors: J
authors: Lawler
authors: Pier
authors: P
authors: Mannucci