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Olson NC, Raffield LM, Moxley AH, et al. Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults. Circ Genom Precis Med. 2021;14(6):e003421doi: 10.1161/CIRCGEN.121.003421.
Olson, N. C., Raffield, L. M., Moxley, A. H., Miller-Fleming, T. W., Auer, P. L., Franceschini, N., Ngo, D., Thornton, T. A., Lange, E. M., Li, Y., Nickerson, D. A., Zakai, N. A., Gerszten, R. E., Cox, N. J., Correa, A., Mohlke, K. L., & Reiner, A. P. (2021). Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults. Circulation. Genomic and precision medicine, 14(6), e003421. https://doi.org/10.1161/CIRCGEN.121.003421
Olson, Nels C, et al. "Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults." Circulation. Genomic and precision medicine vol. 14,6 (2021): e003421. doi: https://doi.org/10.1161/CIRCGEN.121.003421
Olson NC, Raffield LM, Moxley AH, Miller-Fleming TW, Auer PL, Franceschini N, Ngo D, Thornton TA, Lange EM, Li Y, Nickerson DA, Zakai NA, Gerszten RE, Cox NJ, Correa A, Mohlke KL, Reiner AP. Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults. Circ Genom Precis Med. 2021 Dec;14(6):e003421. doi: 10.1161/CIRCGEN.121.003421. Epub 2021 Oct 28. PMID: 34706549; PMCID: PMC8692389.
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Circ Genom Precis Med. 2021 Dec;14(6):e003421. doi: 10.1161/CIRCGEN.121.003421. Epub 2021 Oct 28.

Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults.

Circulation. Genomic and precision medicine

Nels C Olson, Laura M Raffield, Anne H Moxley, Tyne W Miller-Fleming, Paul L Auer, Nora Franceschini, Debby Ngo, Timothy A Thornton, Ethan M Lange, Yun Li, Deborah A Nickerson, Neil A Zakai, Robert E Gerszten, Nancy J Cox, Adolfo Correa, Karen L Mohlke, Alexander P Reiner

Affiliations

  1. Departments of Pathology and Laboratory Medicine (N.C.O., N.A.Z.), University of Vermont, Burlington.
  2. Departments of Genetics (L.M.R., A.H.M., Y.L., K.L.M.), University of North Carolina, Chapel Hill.
  3. Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.W.M.-F., N.J.C.).
  4. Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (P.L.A.).
  5. Epidemiology (N.F.), University of North Carolina, Chapel Hill.
  6. Beth Israel Deaconess Medical Center, Boston, MA (D.N., R.E.G.).
  7. Departments of Biostatistics (T.A.T.), University of Washington, Seattle.
  8. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (E.M.L.).
  9. Biostatistics (Y.L.), University of North Carolina, Chapel Hill.
  10. Computer Science (Y.L.), University of North Carolina, Chapel Hill.
  11. Genome Sciences (D.A.N.), University of Washington, Seattle.
  12. Medicine (N.A.Z.), Larner College of Medicine, University of Vermont, Burlington.
  13. Department of Medicine, University of Mississippi Medical Center, Jackson (A.C.).
  14. Epidemiology (A.P.R.), University of Washington, Seattle.

PMID: 34706549 PMCID: PMC8692389 DOI: 10.1161/CIRCGEN.121.003421

Abstract

BACKGROUND: suPAR (Soluble urokinase plasminogen activator receptor) has emerged as an important biomarker of coagulation, inflammation, and cardiovascular disease (CVD) risk. The contribution of suPAR to CVD risk and its genetic influence in Black populations have not been evaluated.

METHODS: We measured suPAR in 3492 Black adults from the prospective, community-based JHS (Jackson Heart Study). Cross-sectional associations of suPAR with lifestyle and CVD risk factors were assessed, whole-genome sequence data were used to evaluate genetic associations of suPAR, and relationships of suPAR with incident CVD outcomes and overall mortality were estimated over follow-up.

RESULTS: In Cox models adjusted for traditional CVD risk factors, estimated glomerular filtration rate, and CRP (C-reactive protein), each 1-SD higher suPAR was associated with a 21% to 31% increased risk of incident coronary heart disease, heart failure, stroke, and mortality. In the genome-wide association study, 2 missense (rs399145 encoding p.Thr86Ala, rs4760 encoding p.Phe272Leu) and 2 noncoding regulatory variants (rs73935023 within an enhancer element and rs4251805 within the promoter) of

CONCLUSIONS: Our results demonstrate the importance of ancestry-differentiated genetic variation on suPAR levels and indicate suPAR is a CVD biomarker in Black adults.

Keywords: biomarkers; cardiovascular diseases; epidemiologic studies; genome-wide association study; receptors, urokinase plasminogen activator

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