Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
25
08
2023
accepted:
30
10
2023
medline:
4
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
epublish
Résumé
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 APOL1 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 APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 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 APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
Identifiants
pubmed: 38036523
doi: 10.1038/s41467-023-43020-9
pii: 10.1038/s41467-023-43020-9
pmc: PMC10689833
doi:
Substances chimiques
Apolipoprotein L1
0
Apolipoproteins
0
APOL1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7836Subventions
Organisme : NHGRI NIH HHS
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Pays : United States
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Pays : United States
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Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM013061
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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