title: APOL1 nephropathy: from gene to mechanisms of kidney injury.
abstract: The contribution of African ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1). The APOL1 variants appear at a high allele frequency in populations of West African ancestry as a result of apparent adaptive selection of the heterozygous state. Heterozygosity protects from infection with Trypanosoma brucei rhodesiense. This review will describe the role of the approaches in population genetics for the description of APOL1-associated nephropathies and draw inferences as to the biologic mechanisms from genetic epidemiology findings to date. Modifier loci can influence APOL1 risk for the development of kidney disease. 'Second hits', both viral and non-viral, may explain the discrepancy between the remarkably high odds ratios and the low lifetime risks of kidney disease in two allele carriers of APOL1 risk variants. Therapeutic strategies for APOL1-associated nephropathies will require the prevention and treatment of these 'second hits' and the development of drugs to protect the APOL1 downstream renal injury pathways.
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Rambam Health Care Campus, Haifa 3109601, Israel Rambam Health Care Campus, Haifa 3109601, Israel.
authors.forename: Etty
authors.initials: E
authors.lastname: Kruzel-Davila
authors.affiliation: Rambam Health Care Campus, Haifa 3109601, Israel Mayanei HaYeshua Medical Center, Bnei Brak 51544, Israel.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Wasser
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Rambam Health Care Campus, Haifa 3109601, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Aviram
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Rambam Health Care Campus, Haifa 3109601, Israel Rambam Health Care Campus, Haifa 3109601, Israel.
authors.forename: Karl
authors.initials: K
authors.lastname: Skorecki
mesh_terms: D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D004247:DNA
keywords: African American; FSGS; HIV; admixture; hypertension-attributed nephropathy