The <i>UMOD</i> Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease.

Abstract

The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. <i>UMOD</i> is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of <i>UMOD</i> for CKD is clear, because the encoded protein, uromodulin (Tamm-Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in <i>UMOD</i> are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the <i>UMOD</i> paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.