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Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association

Amy Rebecca Bentley1, Ayo P Doumatey, Guanjie Chen

  • 1Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USA.

International Journal of Nephrology
|September 14, 2012
PubMed

Insights

High-density lipoprotein cholesterol (HDLc) levels show varied associations with estimated glomerular filtration rate (eGFR) across ancestries. An inverse relationship was observed in African ancestry populations, potentially linked to APOL1 gene variants.

Area of Science:

  • Nephrology
  • Genetics
  • Cardiovascular Science

Background:

  • Low high-density lipoprotein cholesterol (HDLc) is linked to chronic kidney disease.
  • The relationship between HDLc and estimated glomerular filtration rate (eGFR) in diverse populations is not well understood.

Purpose of the Study:

  • To investigate the association between HDLc and eGFR across different ancestral groups.
  • To explore the role of APOL1 gene variants in the HDLc-eGFR relationship among individuals of African ancestry.

Main Methods:

  • Cross-sectional analysis of HDLc and eGFR in Han Chinese, West Africans, and African Americans.
  • Examination of nationally representative NHANES data from European Americans and African Americans.
  • Investigation of the interaction between APOL1 risk genotype and HDLc-eGFR association in African Americans.

Main Results:

  • HDLc was positively associated with eGFR in Han Chinese and European Americans.
  • An inverse association between HDLc and eGFR was observed in West Africans, African Americans, and in NHANES African Americans.
  • The inverse HDLc-eGFR association in African Americans was significant only among those with the APOL1 risk genotype.

Conclusions:

  • The association between HDLc and eGFR differs significantly by ancestry.
  • Genetic factors, specifically APOL1 variants, may contribute to an inverse HDLc-eGFR association in African ancestry populations.
  • APOL1's influence on kidney disease risk might involve HDLc, suggesting a novel mechanism.

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