The current study identifies a rare coding variant in the CUBN locus and other potential genes associated with albuminuria in individuals with and without diabetes.
The CUBN allele effects on ACR were twice as strong in people with diabetes - a result robust to an optimization-algorithm approach to simulating interactions, validating previously reported gene-diabetes interactions (P≤4x10-5).
Evidence for genetic association exists between a cubilin and a rare megalin variant with diabetes-associated ESRD in populations with recent African ancestry.
We hypothesize that perturbed insulin-Akt cascade in DM leads to alterations in trafficking of megalin and cubilin, which results in urinary cubilin shedding as a prelude to MA in early diabetic nephropathy.