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Gupta, Yask; Friedman, David J.; McNulty, Michelle T.; Khan, Atlas; Lane, Brandon; Wang, Chen; Ke, Juntao; Jin, Gina; Wooden, Benjamin; Knob, Andrea L.; Lim, Tze Y.; Appel, Gerald B.; Huggins, Kinsie; Liu, Lili; Mitrotti, Adele; Stangl, Megan C.; Bomback, Andrew; Westland, Rik; Bodria, Monica; Marasa, Maddalena; Shang, Ning; Cohen, David J.; Crew, Russell J.; Morello, William; [...]

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease

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  • Medientyp: E-Artikel
  • Titel: Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
  • Beteiligte: Gupta, Yask; Friedman, David J.; McNulty, Michelle T.; Khan, Atlas; Lane, Brandon; Wang, Chen; Ke, Juntao; Jin, Gina; Wooden, Benjamin; Knob, Andrea L.; Lim, Tze Y.; Appel, Gerald B.; Huggins, Kinsie; Liu, Lili; Mitrotti, Adele; Stangl, Megan C.; Bomback, Andrew; Westland, Rik; Bodria, Monica; Marasa, Maddalena; Shang, Ning; Cohen, David J.; Crew, Russell J.; Morello, William; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications, 14 (2023) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-43020-9
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the <jats:italic>APOL1</jats:italic> gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the <jats:italic>APOL1</jats:italic> p.N264K missense variant, when co-inherited with the G2 <jats:italic>APOL1</jats:italic> risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the <jats:italic>APOL1</jats:italic> high-risk alleles. These findings have important implications for our understanding of the mechanisms of <jats:italic>APOL1</jats:italic>-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.</jats:p>
  • Zugangsstatus: Freier Zugang