title: APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.
abstract: OBJECTIVE
  We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.
  
  
  RESULTS
  As part of the Cardiovascular Health Study, a population-based cohort of Americans aged ≥65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95% CI, 12.5-14.3) among other African Americans and 13.3 years (95% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.
  
  
  CONCLUSIONS
  APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.). kmukamal@bidmc.harvard.edu.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Tremaglio
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Friedman
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics / Q000401:mortality; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics / Q000401:mortality; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D002423:Cause of Death; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D054624:Health Status Disparities; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000208:ethnology / Q000235:genetics / Q000401:mortality; D010641:Phenotype; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: albuminuria; apolipoproteins; epidemiology; genetics; kidney; myocardial infarction