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APOL1 variants and kidney disease. There is no such thing as a free lunch

Florian Kronenberg1

  • 1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, A-6020 Innsbruck, Austria. florian.kronenberg@i-med.ac.at

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|January 11, 2011
PubMed

Insights

Genetic variations in APOL1, not MYH9, are linked to non-diabetic chronic kidney disease in African-Americans. This APOL1 variation offers protection against Trypanosoma brucei rhodesiense infection.

Area of Science:

  • Genetics
  • Nephrology
  • Epidemiology

Background:

  • The gene region around MYH9 has been discussed for its association with non-diabetic chronic kidney disease (ND-CKD) in African-Americans.
  • Previous research suggested MYH9 as a potential candidate gene, but definitive evidence was lacking.

Purpose of the Study:

  • To investigate the specific genetic variations responsible for the association between the MYH9 gene region and ND-CKD in African-Americans.
  • To explore the evolutionary implications of these genetic variations, particularly regarding infectious disease resistance and susceptibility to kidney disease.

Main Methods:

  • Analysis of genetic variations within the MYH9 gene region and neighboring genes in an African-American cohort.
  • Statistical association studies to link specific genetic variants with ND-CKD.
  • Phylogenetic analysis to assess evidence of positive selection.

Main Results:

  • The strong association with ND-CKD in African-Americans is attributed to genetic variations in APOL1, a gene neighboring MYH9, not MYH9 itself.
  • Evidence suggests positive selection favored APOL1 variants that confer resistance to Trypanosoma brucei rhodesiense infection.
  • These protective variants, however, increase susceptibility to ND-CKD.

Conclusions:

  • APOL1 genetic variations are a primary driver of ND-CKD in African-Americans.
  • The observed genetic pattern reflects a trade-off between resistance to parasitic infection and susceptibility to chronic kidney disease.
  • These findings have significant implications for understanding kidney disease disparities and evolutionary pressures.

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