title: Hemostatic Factors, APOL1 Risk Variants, and the Risk of ESRD in the Atherosclerosis Risk in Communities Study.
abstract: OBJECTIVE
  Hemostatic factors have been associated with kidney function decline, and evidence suggests stronger effects among African Americans. The presence of APOL1 renal risk variants, common in African Americans, might partly underlie this risk difference.
  
  
  METHODS
  A total of 13,337 participants in the Atherosclerosis Risk in Communities study were followed from 1987-1989 until 2010. Participants were categorized into three groups by ancestry and APOL1 risk status: European Americans (n=10,206), African Americans with zero or one APOL1 risk allele (n=2,733), and African Americans with two APOL1 risk alleles (n=398). ESRD events were ascertained through linkage to the US Renal Data System. Cox regression was used to estimate the risk for ESRD associated with hemostatic factors (factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, protein C, and antithrombin III).
  
  
  RESULTS
  There were 232 cases of ESRD over 21.5 years (European Americans, 119; African Americans with zero or one APOL1 risk allele, 94; African Americans with two APOL1 risk alleles, 19). In unadjusted and adjusted analysis of the overall population, higher levels of all hemostatic factors, except antithrombin III, were significantly associated with ESRD (all P<0.05). Factor VIIc had the strongest association (per one interquartile range; adjusted hazard ratio, 1.46; 95% confidence interval, 1.21 to 1.76). With the exception of fibrinogen, the risk associated with each hemostatic factor was stronger in African Americans with two APOL1 risk alleles compared with the other two groups. Statistically significant interactions were seen for factor VIIIc and protein C (interaction between those with two APOL1 risk allele and the other two groups: P<0.02 for factor VIIIc and <0.04 for protein C).
  
  
  CONCLUSIONS
  Higher levels of factor VIIc, VIIIc, fibrinogen, von Willebrand factor, and protein C were associated with ESRD risk, with a significantly stronger association of factor VIIIc and protein C in African Americans with two APOL1 risk alleles.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; atin1@jhu.edu.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tin
authors.affiliation: Divisions of Nephrology and.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Nisa M
authors.initials: NM
authors.lastname: Maruthur
authors.affiliation: Department of Medicine and Department of Population Health Science, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.affiliation: Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina;
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.affiliation: Division of Geriatrics, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.affiliation: Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, Texas; and.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Division of Nephrology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Wen Hong Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D001741:Black or African American / Q000235:genetics* / Q000706:statistics & numerical data; D000483:Alleles; D000990:Antithrombin III / Q000378:metabolism; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D001779:Blood Coagulation Factors; D008075:Lipoproteins, HDL; D011486:Protein C; D014841:von Willebrand Factor; D000990:Antithrombin III; D005169:Factor VIII; D005340:Fibrinogen
keywords: end stage renal disease; genetic renal disease; human genetics; von Willebrand factor