Faculty Collaboration Database

The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels. Blood 2013 Jun 27;121(26):5228-37

Date

03/27/2013

Pubmed ID

23529928

Pubmed Central ID

PMC3722568

DOI

10.1182/blood-2012-10-457507

Scopus ID

2-s2.0-84884180924 (requires institutional sign-in at Scopus site)   98 Citations

Abstract

Genetic variation in or near the C-type lectin domain family 4 member M (CLEC4M) has been associated with plasma levels of von Willebrand factor (VWF) in healthy individuals. CLEC4M is a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR). A total of 491 participants (318 patients with type 1 von Willebrand disease [VWD] and 173 unaffected family members) were genotyped for the CLEC4M VNTR polymorphism. Family-based association analysis on kindreds with type 1 VWD demonstrated an excess transmission of VNTR 6 to unaffected individuals (P = .0096) and an association of this allele with increased VWF:RCo (P = .029). CLEC4M-Fc bound to VWF. Immunofluorescence and enzyme-linked immunosorbent assay demonstrated that HEK 293 cells transfected with CLEC4M bound and internalized VWF. Cells expressing 4 or 9 copies of the CLEC4M neck region VNTR showed reduced interaction with VWF relative to CLEC4M with 7 VNTR (CLEC4M 4%-60% reduction, P < .001; CLEC4M 9%-45% reduction, P = .006). Mice expressing CLEC4M after hydrodynamic liver transfer have a 46% decrease in plasma levels of VWF (P = .0094). CLEC4M binds to and internalizes VWF, and polymorphisms in the CLEC4M gene contribute to variable plasma levels of VWF.

Author List

Rydz N, Swystun LL, Notley C, Paterson AD, Riches JJ, Sponagle K, Boonyawat B, Montgomery RR, James PD, Lillicrap D

Author

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Animals
Case-Control Studies
Child
Child, Preschool
DNA
Enzyme-Linked Immunosorbent Assay
Family
Female
Flow Cytometry
Genome-Wide Association Study
Genotype
HEK293 Cells
Humans
Immunoenzyme Techniques
Infant
Lectins, C-Type
Linkage Disequilibrium
Liver
Male
Mice
Middle Aged
Minisatellite Repeats
Polymerase Chain Reaction
Polymorphism, Genetic
Young Adult
von Willebrand Diseases
von Willebrand Factor