APOL1: The Balance Imposed by Infection, Selection, and Kidney Disease. Issue 8 (August 2018)

• Record Type: Journal Article
• Authors: Beckerman, Pazit; Susztak, Katalin
• Is Part Of: Trends in molecular medicine. Volume 24:Issue 8(2018)
• Page Start: 682
• Page End: 695
• Publication Date: 2018-08
• Subjects: Apolipoprotein 1 -- chronic kidney disease -- genetics; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2018.05.008
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Chronic kidney disease (CKD) affects millions of people and constitutes a major health and financial burden worldwide. People of African descent are at an increased risk of developing kidney disease, which is mostly explained by two variants in the Apolipoprotein L1 (APOL1) gene that are found only in people of west African origin. It is hypothesized that these variants were genetically selected due to the protection they afford against African sleeping sickness, caused by the parasite Trypanosoma brucei . Targeting mutant APOL1 could have substantial therapeutic potential for treating kidney disease. In this review, we will describe the intriguing interplay between microbiology, genetics, and kidney disease as revealed in APOL1-associated kidney disease, discuss APOL1-induced cytotoxicity and its therapeutic implications. Highlights: Nucleotide variants in the Apolipoprotein L1 (APOL1) gene contribute to the increased risk of kidney disease in people of African ancestry. It is believed that the high allele frequency of these variants is due to the resistance they confer against the disease-causing trypanosome species, which is implicated in human African sleeping sickness. The mechanism by which APOL1 causes kidney disease is not fully understood. Experiments suggest that mutant APOL1 proteins create ion channels in membranes, disrupt the endo-lysosomal function, alter autophagy, and induce inflammatory cell death and podocyte damage.