title: Analytical Validation of a Personalized Medicine APOL1 Genotyping Assay for Nondiabetic Chronic Kidney Disease Risk Assessment.
abstract: The incidence of chronic kidney disease (CKD) varies by ancestry, with African Americans (AA) having a threefold to fourfold higher rate than whites. Notably, two APOL1 alleles, termed G1 [c.(1072A>G; 1200T>G)] and G2 (c.1212_1217del6), are strongly associated with higher rates of nondiabetic CKD and an increased risk for hypertensive end-stage renal disease. This has prompted the opportunity to implement APOL1 testing to identify at-risk patients and modify other risk factors to reduce the progression of CKD to end-stage renal disease. We developed an APOL1 genotyping assay using multiplex allele-specific primer extension, and validated using 58 positive and negative controls. Genotyping results were completely concordant with Sanger sequencing, and both triplicate interrun and intrarun genotyping results were completely concordant. Multiethnic APOL1 allele frequencies were also determined by genotyping 7059 AA, Hispanic, and Asian individuals from the New York City metropolitan area. The AA, Hispanic, and Asian APOL1 G1 and G2 allele frequencies were 0.22 and 0.13, 0.037 and 0.025, and 0.013 and 0.004, respectively. Notably, approximately 14% of the AA population carried two risk alleles and are at increased risk for CKD, compared with <1% of the Hispanic and Asian populations. This novel APOL1 genotyping assay is robust and highly accurate, and represents one of the first personalized medicine clinical genetic tests for disease risk prediction.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jinglan.zhang@bcm.edu.
authors.forename: Jinglan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Fedick
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wasserman
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Geping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Lisa
authors.initials: L
authors.lastname: Edelmann
authors.affiliation: Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kornreich
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: stuart.scott@mssm.eddsu.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Scott
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D001213:Asian / Q000235:genetics; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D009519:New York City / Q000208:ethnology; D057285:Precision Medicine / Q000379:methods; D051436:Renal Insufficiency, Chronic / Q000235:genetics*
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL