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Epigenetic associations with kidney disease in individuals of African ancestry with APOL1 high-risk genotypes and Human Immunodeficiency Virus

  1. Author:
    Hung, Rachel K Y
    Costeira, Ricardo
    Chen, Junyu [ORCID]
    Schlosser, Pascal
    Grundner-Culemann, Franziska
    Booth, John W
    Sharpe, Claire C
    Bramham, Kate
    Sun, Yan V
    Marconi, Vincent C [ORCID]
    Teumer, Alexander [ORCID]
    Winkler,Cheryl
    Post, Frank A
    Bell, Jordana T

  2. Author Address

    1Department of HIV and Sexual Health, King's College Hospital, London, UK. 2Department of Twin Research & Genetic Epidemiology, King's College London, UK. 3Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. 4Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. 5Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 6Department of Renal Medicine, Bart's Health NHS Foundation Trust, London, UK. 7Department of Renal Medicine, King's College Hospital, London, UK. 8Atlanta Veterans Affairs Health Care System, Decatur, Georgia, USA. 9Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States. 10School of Medicine, Emory University, Atlanta, GA, United States. 11DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. 12Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. 13Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland. 14Cancer Innovation Laboratory, Center for Cancer Research and the Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.
    1. Year: 2024
    2. Date: Oct 24
    3. Epub Date: 2024 10 24
  2. Journal: Nephrology, Dialysis, Transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  4. Type of Article: Article
  1. Abstract:

    Apolipoprotein L1 (APOL1) high-risk variants are major determinants of chronic kidney disease (CKD) in people of African ancestry. Previous studies have identified epigenetic changes in relation to kidney function and CKD, but not in individuals with APOL1 high-risk genotypes. We conducted an epigenome-wide analysis of CKD and estimated glomerular filtration rate (eGFR) in in people of African ancestry and APOL1 high-risk genotypes with HIV. DNA methylation profiles from peripheral blood mononuclear cells of 119 individuals with APOL1 high-risk genotypes (mean age 48 years, 49% female, median CD4 count 515 cells/mm3, 90% HIV-1 RNA < 200 copies/mL, 23% with CKD) were obtained by Illumina MethylationEPIC BeadChip. Differential methylation analysis of CKD considered technical and biological covariates. We also assessed associations with eGFR. Replication was pursued in three independent multi-ancestry cohorts with and without HIV. DNA methylation levels at 14 regions were associated with CKD. The strongest signals were located in SCARB1, DNAJC5B and C4orf50. Seven of the 14 signals also associated with eGFR, and most showed evidence for a genetic basis. Four signals (in SCARB1, FRMD4A, CSRNP1 and RAB38) replicated in other cohorts, and 11 previously reported epigenetic signals for kidney function or CKD replicated in our cohort. We found no significant DNA methylation signals in, or near, the APOL1 promoter region. We report several novel as well as previously reported epigenetic associations with CKD and eGFR in individuals with HIV having APOL1 high-risk genotypes. Further investigation of pathways linking DNA methylation to APOL1 nephropathies is warranted. © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.

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  2. DOI: 10.1093/ndt/gfae237
  3. PMID: 39448372
  4. PII : 7840394

Library Notes

  1. Fiscal Year: FY2024-2025
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