Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project. Blood 2013 Jul 25;122(4):590-7

Date

05/22/2013

Pubmed ID

23690449

Pubmed Central ID

PMC3724194

DOI

10.1182/blood-2013-02-485094

Scopus ID

2-s2.0-84886901150 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

Several rare European von Willebrand disease missense variants of VWF (including p.Arg2185Gln and p.His817Gln) were recently reported to be common in apparently healthy African Americans (AAs). Using data from the NHLBI Exome Sequencing Project, we assessed the association of these and other VWF coding variants with von Willebrand factor (VWF) and factor VIII (FVIII) levels in 4468 AAs. Of 30 nonsynonymous VWF variants, 6 were significantly and independently associated (P < .001) with levels of VWF and/or FVIII. Each additional copy of the common VWF variants encoding p.Thr789Ala or p.Asp1472His was associated with 6 to 8 IU/dL higher VWF levels. The VWF variant encoding p.Arg2185Gln was associated with 7 to 13 IU/dL lower VWF and FVIII levels. The type 2N-related VWF variant encoding p.His817Gln was associated with 17 IU/dL lower FVIII level but normal VWF level. A novel, rare missense VWF variant that predicts disruption of an O-glycosylation site (p.Ser1486Leu) and a rare variant encoding p.Arg2287Trp were each associated with 30 to 40 IU/dL lower VWF level (P < .001). In summary, several common and rare VWF missense variants contribute to phenotypic differences in VWF and FVIII among AAs.

Author List

Johnsen JM, Auer PL, Morrison AC, Jiao S, Wei P, Haessler J, Fox K, McGee SR, Smith JD, Carlson CS, Smith N, Boerwinkle E, Kooperberg C, Nickerson DA, Rich SS, Green D, Peters U, Cushman M, Reiner AP, NHLBI Exome Sequencing Project

Author

Paul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




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

Adult
Aged
Blood Chemical Analysis
Cohort Studies
Exome
Factor VIII
Female
Gene Frequency
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation, Missense
National Heart, Lung, and Blood Institute (U.S.)
Open Reading Frames
Polymorphism, Single Nucleotide
United States
Young Adult
von Willebrand Factor