Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria

What is it about?

Hematuria, the presence of blood in the urine, can be a sign of disease of the lower urinary tract or of kidney disease. However, the study of hematuria has been limited and there are still many questions to explore. The availability of large, population-based datasets that include genetic and clinical data allow us to better characterize and understand the risk factors leading to hematuria. In this study, our goal was to combine multiple layers of genetic information to investigate potential molecular mechanisms contributing to hematuria. We identified a structural sequence change in the messenger RNA of the gene COL4A4, which could alter the protein function to be associated with hematuria. The COL4A4 gene is an important component for optimal kidney function. Aside from identifying an association with hematuria, we identified the same structural sequence change in a subset of patients with kidney disease from an independent cohort. Finally, we demonstrated using a molecular assay, that the same structural sequence change produces a dysfunctional protein that can could affect kidney function. Our results highlight the value of investigating the role of genetic variants and the molecular mechanisms by which they contribute to kidney disease.

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