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

Trends Mol Med. 2018 Aug;24(8):682-695. doi: 10.1016/j.molmed.2018.05.008. Epub 2018 Jun 7.

Abstract

Chronic kidney disease (CKD) affects millions of people and constitutes a major health and financial burden worldwide. People of African descent are at an increased risk of developing kidney disease, which is mostly explained by two variants in the Apolipoprotein L1 (APOL1) gene that are found only in people of west African origin. It is hypothesized that these variants were genetically selected due to the protection they afford against African sleeping sickness, caused by the parasite Trypanosoma brucei. Targeting mutant APOL1 could have substantial therapeutic potential for treating kidney disease. In this review, we will describe the intriguing interplay between microbiology, genetics, and kidney disease as revealed in APOL1-associated kidney disease, discuss APOL1-induced cytotoxicity and its therapeutic implications.

Keywords: Apolipoprotein 1; chronic kidney disease; genetics.

Publication types

  • Review

MeSH terms

  • Alleles
  • Animals
  • Apolipoprotein L1 / genetics*
  • Apolipoprotein L1 / metabolism*
  • Disease Susceptibility
  • Endocytosis
  • Epistasis, Genetic
  • Gene-Environment Interaction
  • Genetic Variation
  • Host-Parasite Interactions
  • Humans
  • Infections / etiology*
  • Infections / metabolism*
  • Inheritance Patterns
  • Kidney Diseases / etiology*
  • Kidney Diseases / metabolism*
  • Mutation
  • Podocytes / metabolism
  • Protein Transport
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / metabolism
  • Selection, Genetic*
  • Trypanosoma / physiology

Substances

  • Apolipoprotein L1