Month: January 2022

The common H202D variant in GDF-15 does not affect its bioactivity but can significantly interfere with measurement of its circulating levels

Yanislava Karusheva, Matt Ratcliff, Audrey Melvin, Alexander Moerseburg, Naveed Sattar, Peter Barker, Keith Burling, Anna Backmark, Robert Roth, Lutz Jermutus, Esther Guiu-Jurado, Matthias Blueher, Paul Welsh, Marko Hyvönen, Stephen O’Rahilly

MedRxiv preprint DOI: 022.01.03.22268655

GDF15 bioactivity

Abstract

Genetic variants in proteins can interfere with measurement of their circulating concentrations. Given the growing biomedical importance of GDF-15, we wished to establish whether a common histidine to aspartate variant present in position 6 of the mature GDF-15 protein (H202D variant) interfered with its measurement by two commonly used immunoassays. We first examined the detectability of recombinant monomers, homodimers and heterodimers of GDF-15 by assays and/or reagents used in two widely used immunoassays (Roche Elecsys GDF-15 and the R&D antibody combinations used in their Quantikine and DuoSet ELISAs). The Roche assay detected the H and D containing peptides similarly but the assays based on the R&D reagents consistently underreported concentrations of the D-containing variant peptide. Measurements of plasma concentrations of GDF-15 in genotyped human participants showed that the R&D reagents reported values in heterozygotes were ~25% lower, and in homozygotes, 50% lower than the Roche assay. Continue reading →

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