Kidney Disease-Associated APOL1 Variants Have Dose-Dependent, Dominant Toxic Gain-of-Function.

ABSTRACT:

Background

Two coding renal risk variants (RRVs) of the APOL1 gene (G1 and G2) are associated with large increases in CKD rates among populations of recent African descent, but the underlying molecular mechanisms are unknown. Mammalian cell culture models are widely used to study cytotoxicity of RRVs, but results have been contradictory. It remains unclear whether cytotoxicity is RRV-dependent or driven solely by variant-independent overexpression. It is also unknown whether expression of the reference APOL1 allele, the wild-type G0, could prevent cytotoxicity of RRVs.

Methods

We generated tetracycline-inducible APOL1 expression in human embryonic kidney HEK293 cells and examined the effects of increased expression of APOL1 (G0, G1, G2, G0G0, G0G1

SUBMITTER: Datta S 

PROVIDER: S-EPMC7461666 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature