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