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The following is a summary of “Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria,” published in the August 2024 issue of Nephrology by Lona-Durazo et al.
Hematuria is a sign of glomerular disease and might be linked to kidney failure.
Researchers conducted a retrospective study to identify genetic and transcriptomic mechanisms associated with hematuria by analyzing data from the UK Biobank and GTEx kidney cortex samples.
They collected and merged genetic data from the UK Biobank with predicted gene expression and splicing from 65 GTEx kidney cortex samples in a transcriptome-wide association study (TWAS) to uncover more potential biological mechanisms affecting hematuria.
The results showed that the TWAS using kidney cortex data found significant associations for 5 genes related to expression and 3 splicing events. Notably, skipping COL4A4 exon 27, predicted by rs11898094 (13% frequency), was linked to hematuria and urinary albumin excretion. The same variant was validated using NEPTUNE glomeruli-derived mRNA transcriptomics data in 245 individuals. The loss of exon 27’s functional significance was shown using the split NanoLuc-based α3α4α5(IV) heterotrimer assay, which quantified type IV collagen heterotrimer formation via luminescence. The specific causal splicing variant for this skipping event has yet to be identified.
Investigators concluded that combining different data types helped identify a possible splicing event linked to hematuria and albuminuria. This finding provides new insights into the genetic factors that may influence these kidney-related conditions.
Source: journals.lww.com/jasn/abstract/9900/association_of_genetically_predicted_skipping_of.408.aspx
