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APOL1 Nephropathy Risk Variants Through the Life Course: A Review.

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Summary
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Two apolipoprotein L1 (APOL1) gene risk variants (RVs) significantly increase kidney disease risk in individuals of African descent. These APOL1 variants interact with environmental factors throughout life, impacting long-term health outcomes and kidney failure progression.

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Area of Science:

  • Genetics
  • Nephrology
  • Immunology

Background:

  • Two variant alleles of the apolipoprotein L1 (APOL1) gene, known as risk variants (RVs), are a primary cause of kidney disease in individuals of African descent.
  • The APOL1 protein plays a role in innate immunity, potentially offering protection against various pathogens.
  • Carrying APOL1 RVs can initiate disease processes in utero, exacerbated by environmental exposures, infections, and systemic diseases, collectively termed 'second hits'.

Purpose of the Study:

  • To review APOL1-associated diseases from a life-course perspective.
  • To examine how early-life 'second hits' influence long-term health outcomes in individuals with APOL1 RVs.
  • To discuss the implications of APOL1 RVs on kidney disease progression and transplant outcomes.

Main Methods:

  • This is a review article, synthesizing existing research on APOL1 gene variants and associated diseases.
  • The review adopts a life-course approach, analyzing the impact of APOL1 RVs across different life stages.
  • It integrates information on genetic predisposition, environmental interactions, and clinical outcomes.

Main Results:

  • APOL1 RVs are a major determinant of kidney disease burden in individuals of African descent.
  • APOL1-related kidney disease often manifests in adolescents and young adults, with a higher likelihood of progression to kidney failure in RV carriers.
  • APOL1 RVs are associated with adverse outcomes in kidney transplantation for both donors and recipients.

Conclusions:

  • APOL1 RVs significantly contribute to kidney disease and influence health across the lifespan.
  • Interactions between APOL1 RVs and environmental factors ('second hits') are critical in modifying disease risk and progression.
  • Further research is essential to identify risk and protective factors for APOL1 RVs throughout life and to develop targeted treatments for APOL1-associated nephropathy.