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APOL1 Nephropathy Risk Alleles and Risk of Sepsis in Blacks

Ninad S Chaudhary1, Justin X Moore1,2, Neil A Zakai3

  • 1Departments of Epidemiology.

Clinical Journal of the American Society of Nephrology : CJASN
|November 10, 2019
PubMed

Insights

Apolipoprotein L1 (APOL1) gene variants increase sepsis risk in Black adults. This common genetic trait, linked to kidney disease, also heightens susceptibility to infections.

Area of Science:

  • Genetics and Genomics
  • Infectious Diseases
  • Nephrology

Background:

  • Apolipoprotein L1 (APOL1) nephropathy risk alleles are established risk factors for chronic kidney disease (CKD) in individuals of Black African ancestry.
  • APOL1 possesses innate immune functions, but its association with infectious outcomes, such as sepsis, remains underexplored.
  • Understanding the role of APOL1 in infection risk is crucial for public health, particularly in populations with high prevalence of these alleles.

Purpose of the Study:

  • To investigate the association between APOL1 nephropathy risk alleles and the risk of developing sepsis.
  • To examine these associations in a large cohort of Black adults.
  • To determine if the association varies by diabetes or CKD status.

Main Methods:

  • A cohort of 10,366 Black participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study was analyzed.
  • APOL1 risk allele carriage was assessed, and incident sepsis events were tracked over a median follow-up of 6.5 years.
  • Cox proportional hazards models, adjusted for demographics, comorbidities, and ancestry, were used to evaluate genetic associations under recessive, dominant, and additive models.

Main Results:

  • The prevalence of APOL1 risk alleles was high: 13% had two, 46% had one, and 42% had zero risk alleles.
  • No significant association was found between APOL1 genotype and sepsis risk under recessive models.
  • However, significant associations were observed under dominant (HR, 1.55; 95% CI, 1.13-2.11) and additive (HR per variant allele, 1.25; 95% CI, 1.02-1.53) models, independent of diabetes or CKD status.

Conclusions:

  • Carriage of APOL1 nephropathy risk alleles is common in community-dwelling Black adults.
  • These APOL1 risk alleles are associated with an increased risk of sepsis in this population.
  • The findings highlight a potential genetic predisposition to infection related to APOL1 variants.
Abstract

Keywords:
African Americansadultallelesapolipoprotein L1chronic kidney diseasechronic renal insufficiencyclinical epidemiologyconfidence intervalsdiabetes mellitusethnicityfollow-up studiesgenetic modelsgenetic renal diseasegenotypehumansindependent livingodds ratioproportional hazards modelsrisksepsisstroke

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