Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress.

ABSTRACT:

Background

High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.

Methods and results

Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P<5×10(-8)) was identified with 2 single-nucleotide polymorphisms within the SVIL gene (chromosome 10p11.23) in African Americans but not European Americans. Microarray analyses of human platelet RNA demonstrated the presence of SVIL isoform 1 (supervilli

SUBMITTER: Edelstein LC 

PROVIDER: S-EPMC3515852 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature