☆ 4.6 Article

Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans

AMERICAN JOURNAL OF HEMATOLOGY (2015)

期刊

AMERICAN JOURNAL OF HEMATOLOGY

卷 90, 期 6, 页码 534-540

出版社

WILEY-BLACKWELL

DOI: 10.1002/ajh.24005

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Hematology

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NIH [R01-HL095603, R01-HL59367]

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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 ABO 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 KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 x 10(-7) in EAs and P=3.88 x 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 x 10(-9) in EAs and P=2.98 x 10(-2) in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 x 10(-10)), with VWF rs1800380 in AAs (P=5.62 x 10(-11)), and with MAT1A rs2236568 in AAs (P=1.69 x 10(-6)). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF 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. (c) 2015 Wiley Periodicals, Inc.

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