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Hemostatic Factors, APOL1 Risk Variants, and the Risk of ESRD in the Atherosclerosis Risk in Communities Study

Adrienne Tin1, Morgan E Grams2, Nisa M Maruthur3

  • 1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; atin1@jhu.edu.

Clinical Journal of the American Society of Nephrology : CJASN
|April 19, 2015
PubMed

Insights

Higher levels of blood clotting factors increase the risk of end-stage renal disease (ESRD). This risk is significantly amplified in African Americans with specific APOL1 gene variants.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Genetics

Background:

  • Hemostatic factors are linked to kidney function decline.
  • African Americans exhibit a disproportionately higher risk of kidney disease progression.
  • APOL1 renal risk variants, prevalent in African Americans, may explain this disparity.

Purpose of the Study:

  • To investigate the association between hemostatic factors and end-stage renal disease (ESRD) risk.
  • To examine whether APOL1 risk variants modify this association in African Americans.

Main Methods:

  • Analysis of 13,337 Atherosclerosis Risk in Communities study participants (1987-2010).
  • Categorization by ancestry and APOL1 risk alleles: European Americans, African Americans (0-1 allele), and African Americans (2 alleles).
  • Cox regression used to assess ESRD risk associated with six hemostatic factors.

Main Results:

  • Higher levels of factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, and protein C were associated with increased ESRD risk.
  • Factor VIIc demonstrated the strongest association.
  • The association between most hemostatic factors and ESRD was significantly stronger in African Americans with two APOL1 risk alleles.

Conclusions:

  • Elevated levels of specific hemostatic factors are risk factors for ESRD.
  • APOL1 risk variants significantly amplify the ESRD risk associated with hemostatic factors in African Americans, particularly for factor VIIIc and protein C.
Abstract

Keywords:
end stage renal diseasegenetic renal diseasehuman geneticsvon Willebrand factor

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