Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans
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Out of Africa: Kidney disease is more common in African Americans than in Americans of European descent, and genetics is likely to be a major contributing factor. Genovese et al. (p. 841 , published online 15 July) now show that African Americans who carry specific sequence variants in a gene on chromosome 22 encoding apolipoprotein L-1 (APOL1) have an increased risk of developing hypertension-attributed end-stage kidney disease or focal segmental glomerulosclerosis. These variants are absent from European chromosomes. Among the functions ascribed to APOL1 is the ability to lyse and kill trypanosomes. Intriguingly, APOL1 derived from the risk alleles, but not the “wild-type” allele, killed Trypanosoma brucei rhodesiense , which causes African sleeping sickness.
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For a few risk alleles, hallmarks of balancing selection reflect increased carrier survival, usually through protection from infectious diseases.
“For a few risk alleles, hallmarks of balancing selection reflect increased carrier survival, usually through protection from infectious diseases.”
From A brief history of human disease genetics (2020) · cites this paper as [57]
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- Authors
- Genovese, G., Friedman, D. J., Ross, M. D., Lecordier, L., Uzureau, P., Freedman, B. I., Bowden, D. W., Langefeld, C. D., Oleksyk, T. K., Uscinski Knob, A. L., Bernhardy, A. J., Hicks, P. J., Nelson, G. W., Vanhollebeke, B., Winkler, C. A., Kopp, J. B., Pays, E., & Pollak, M. R.
- Affiliations
- Dartmouth College (US)
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Université Libre de Bruxelles (BE)
- Wake Forest University Health Sciences (US)
- Department of Biology, University of Puerto Rico at Mayaguez, Mayaguez, Puerto Rico 00681.
- Renal Division, Department of Medicine, Brigham and Women’s Hospital (BWH), Boston, MA 02215, USA.
- National Institutes of Health (US)
- Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, B-6041 Gosselies, Belgium.
- National Cancer Institute (US)
- Broad Institute (US)
- Corresponding author
- Genovese, Giulio
- Friedman, David J.
- Pays, Etienne
- Pollak, Martin R.
- ORCID
- Venue
- Science
- Published
- 2010-08-13
- Volume
- 329
- Issue
- 5993
- Pages
- 841-845
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2980843
- OpenAlex
- W2124641083
- Cited by
- 2,028
- References
- 24
- Citations by year
- 2026: 85 · 2025: 108 · 2024: 111 · 2023: 142 · 2022: 131 · 2021: 134 · 2020: 127 · 2019: 135 · 2018: 123 · 2017: 141 · 2016: 130 · 2015: 139 · 2014: 136 · 2013: 117 · 2012: 127
- FWCI
- 95.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Heart, Lung, and Blood Institute (R01 HL 56266, R01HL056266)
- National Cancer Institute (Z01BC010022, HHSN261200800001E), ZIABC010022)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK066358, K08DK076868, R01DK053591, R01DK54931, R01DK070941, R01DK084149, R01DK054931, Z01DK043308)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- APOL1, focal segmental glomerulosclerosis, end-stage renal disease, hypertension, African Americans, positive selection, haplotypes, Trypanosoma brucei rhodesiense
- MeSH terms
- Apolipoprotein L1, Africa, Alleles, Apolipoproteins, Black or African American, Gene Frequency, Glomerulosclerosis, Focal Segmental, Haplotypes, Humans, Hypertension, Immunity, Innate, Kidney Failure, Chronic, Lipoproteins, HDL, Recombinant Proteins, Selection, Genetic, Trypanosomiasis, African, Cohort Studies, Linkage Disequilibrium, Logistic Models, Case-Control Studies, Trypanosoma brucei rhodesiense, Sequence Deletion, Myosin Heavy Chains, Genetic Predisposition to Disease, Molecular Motor Proteins, Polymorphism, Single Nucleotide, Genetic Association Studies
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