Association of trypanolytic ApoL1 variants with kidney disease in African Americans

Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. Epub 2010 Jul 15.

Abstract

African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa
  • African Americans / genetics*
  • Alleles
  • Apolipoprotein L1
  • Apolipoproteins / blood
  • Apolipoproteins / genetics*
  • Apolipoproteins / metabolism
  • Case-Control Studies
  • Cohort Studies
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glomerulosclerosis, Focal Segmental / ethnology
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Haplotypes
  • Humans
  • Hypertension / complications
  • Immunity, Innate
  • Kidney Failure, Chronic / ethnology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics*
  • Linkage Disequilibrium
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / genetics*
  • Lipoproteins, HDL / metabolism
  • Logistic Models
  • Molecular Motor Proteins / genetics
  • Myosin Heavy Chains / genetics
  • Polymorphism, Single Nucleotide*
  • Recombinant Proteins / metabolism
  • Selection, Genetic
  • Sequence Deletion
  • Trypanosoma brucei rhodesiense / metabolism*
  • Trypanosomiasis, African / genetics
  • Trypanosomiasis, African / parasitology

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Recombinant Proteins
  • Myosin Heavy Chains