title: APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy Study.
abstract: APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.
authors.affiliation: Centre for Chronic Disease, The University of Queensland, Brisbane, Queensland, Australia; w.hoy@uq.edu.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Hoy
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughson
authors.affiliation: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland;
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.affiliation: Centre for Chronic Disease, The University of Queensland, Brisbane, Queensland, Australia;
authors.forename: Susan A
authors.initials: SA
authors.lastname: Mott
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, Australia; and.
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Lidos Biomedical Inc., Frederick National Laboratory, Frederick, Maryland.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: APOL1 risk alleles; African Americans; glomerular enlargement; glomerular number