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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
Summary

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

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

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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.