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Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States.
da Silva Francisco, Ronaldo; Punj, Sumit; Vincent, Lisa; Sanapareddy, Nina; Bhalla, Vivek; Chertow, Glenn M; Keen-Kim, Dianne; Charu, Vivek.
Afiliación
  • da Silva Francisco R; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
  • Punj S; Natera, Inc. 201 Industrial Boulevard, San Carlos, California, USA.
  • Vincent L; Natera, Inc. 201 Industrial Boulevard, San Carlos, California, USA.
  • Sanapareddy N; Natera, Inc. 201 Industrial Boulevard, San Carlos, California, USA.
  • Bhalla V; Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
  • Chertow GM; Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
  • Keen-Kim D; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
  • Charu V; Natera, Inc. 201 Industrial Boulevard, San Carlos, California, USA.
Kidney Int Rep ; 9(9): 2667-2676, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39291188
ABSTRACT

Introduction:

Among individuals with high-risk APOL1 genotypes, the lifetime risk of developing kidney failure is ∼15%, indicating that other genetic variants or nongenetic modifiers likely contribute substantially to an individual patient's risk of progressive kidney disease. Here, we estimate the prevalence and distribution of Mendelian kidney diseases among patients with high-risk APOL1 genotypes undergoing commercial genetic testing in the United States.

Methods:

We analyzed clinical exome sequencing data from 15,181 individuals undergoing commercial genetic testing for Mendelian kidney disease in the United States from 2020 to 2021. We identified patients with high-risk APOL1 genotypes by the presence of G1/G1, G1/G2, or G2/G2 alleles. Patients carrying single risk APOL1 alleles were identified as G1/G0, G2/G0; the remainder of patients were G0/G0. We estimated the prevalence and distribution of Mendelian kidney disease stratified by APOL1 genotype and genetically predicted ancestry.

Results:

Of 15,181 patients, 3119 had genetic testing results consistent with a molecular diagnosis of Mendelian kidney disease (20.5%). Of 15,181 patients, 1035 (6.8%) had high-risk APOL1 genotypes. Among patients with recent genomic African ancestry, the prevalence of Mendelian kidney diseases was lower in those with high-risk APOL1 genotypes (9.6%; n = 91/944) compared with single risk APOL1 allele carriers (13.6%; n = 198/1453) and those with G0/G0 APOL1 genotypes (16.6%; n = 213/1281). Among patients with Mendelian kidney disease and recent genomic African ancestry, we observed differences in the prevalence of pathogenic/likely pathogenic variants in PKD1 (19.8% in high-risk vs. 30.2% in low-risk genotypes), and COL4A4 (24.2% in high-risk vs. 10.5% in low-risk genotypes).

Conclusion:

In this selected population of patients undergoing clinical genetic testing, we found evidence of Mendelian kidney disease in ∼10% patients with high-risk APOL1 genotypes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Kidney Int Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Kidney Int Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos