title: Most ApoL1 Is Secreted by the Liver.
abstract: Two coding sequence variants in theAPOL1gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.
authors.affiliation: Division of Nephrology, Department of Medicine and.|Harvard Medical School, Boston, Massachusetts.
authors.forename: Khuloud
authors.initials: K
authors.lastname: Shukha
authors.affiliation: Harvard Medical School, Boston, Massachusetts.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; and.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mueller
authors.affiliation: Harvard Medical School, Boston, Massachusetts.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; and.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Harvard Medical School, Boston, Massachusetts.|Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Division of Nephrology, Department of Medicine and.|Harvard Medical School, Boston, Massachusetts.
authors.forename: David J
authors.initials: DJ
authors.lastname: Friedman
authors.affiliation: Division of Nephrology, Department of Medicine and mpollak@bidmc.harvard.edu.|Harvard Medical School, Boston, Massachusetts.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
authors.affiliation: Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: Pathophysiology of Renal Disease and Progression; apoptosis; focal segmental glomerulosclerosis; kidney disease; transplantation