Gene‐centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans. Issue 6 (1st April 2015)

• Record Type: Journal Article
• Authors: Tang, Weihong; Cushman, Mary; Green, David; Rich, Stephen S.; Lange, Leslie A.; Yang, Qiong; Tracy, Russell P.; Tofler, Geoffrey H.; Basu, Saonli; Wilson, James G.; Keating, Brendan J.; Weng, Lu‐Chen; Taylor, Herman A.; Jacobs, David R.; Delaney, Joseph A.; Palmer, Cameron D.; Young, Taylor; Pankow, James S.; O'Donnell, Christopher J.; Smith, Nicholas L.; Reiner, Alexander P.; Folsom, Aaron R.
• Is Part Of: American journal of hematology. Volume 90:Issue 6(2015:Jun.)
• Page Start: 534
• Page End: 540
• Publication Date: 2015-04-01
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24005
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with <italic>ABO</italic> blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European‐American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50, 000 gene‐centric single nucleotide polymorphisms (SNPs) in 18, 556 European Americans (EAs) and 5, 047 African Americans (AAs) from five population‐based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with <italic>KNG1</italic> (most significantly associated SNP rs710446, Ile581Thr, <italic>P</italic> = 5.10 × 10<sup>−7</sup> in EAs and <italic>P</italic> = 3.88 × 10<sup>−3</sup> in AAs) and <italic>VWF</italic> rs7962217 (Gly2705Arg, <italic>P</italic> = 6.30 × 10<sup>−9</sup> in EAs and <italic>P</italic> = 2.98 × 10<sup>−2</sup> in AAs). Significant associations for FVIII:C were also observed with <italic>F8</italic>/<italic>TMLHE</italic> region SNP rs12557310 in EAs (<italic>P</italic> = 8.02 × 10<sup>−10</sup>), with <italic>VWF</italic> rs1800380 in AAs (<italic>P</italic> = 5.62 × 10<sup>−11</sup>), and with <italic>MAT1A</italic> rs2236568 in AAs (<italic>P</italic> = 1.69 × 10<sup>−6</sup>). We replicated previously reported associations of FVIII:C and VWF:Ag with the <italic>ABO</italic> blood group, <italic>VWF</italic> rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and <italic>VWF</italic> rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs. Am. J. Hematol. 90:534–540, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>