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APOL1: The Balance Imposed by Infection, Selection, and Kidney Disease

Pazit Beckerman1, Katalin Susztak2

  • 1Renal-Electrolyte and Hypertension Division of Department of Medicine, and Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Nephrology and Hypertension, Sheba Medical Center, Tel Hashomer, Israel.

Trends in Molecular Medicine
|June 11, 2018
PubMed

Insights

Genetic variants in the Apolipoprotein L1 (APOL1) gene increase kidney disease risk in people of African descent. Targeting mutant APOL1 offers potential therapeutic strategies for APOL1-associated kidney disease.

Area of Science:

  • Nephrology
  • Genetics
  • Microbiology

Background:

  • Chronic kidney disease (CKD) presents a significant global health and economic challenge.
  • Individuals of African descent exhibit a higher predisposition to kidney disease, primarily linked to specific Apolipoprotein L1 (APOL1) gene variants.
  • These APOL1 variants are hypothesized to have been selected due to conferring protection against African sleeping sickness.

Purpose of the Study:

  • To explore the connection between microbiology, genetics, and kidney disease within the context of APOL1-associated kidney disease.
  • To discuss the mechanisms of APOL1-induced cytotoxicity.
  • To examine the therapeutic implications of targeting APOL1.

Main Methods:

  • Review of existing literature on APOL1 gene variants and kidney disease.
  • Analysis of the interplay between Trypanosoma brucei infection and APOL1 genetics.
  • Examination of cellular mechanisms underlying APOL1 nephrotoxicity.

Main Results:

  • APOL1 gene variants are strongly associated with increased risk and progression of kidney disease in specific populations.
  • The evolutionary selection of APOL1 variants may be tied to pathogen resistance.
  • Understanding APOL1 cytotoxicity is crucial for developing targeted therapies.

Conclusions:

  • APOL1-associated kidney disease is a complex condition influenced by genetic and environmental factors.
  • Targeting mutant APOL1 presents a promising avenue for novel therapeutic interventions in kidney disease.
  • Further research into APOL1's role in kidney pathophysiology is warranted.

Keywords:
Apolipoprotein 1chronic kidney diseasegenetics

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