{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T09:54:13Z","timestamp":1792835653157,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,29]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n There is growing interest in the measurement of growth differentiation factor 15 (GDF-15) in a range of disorders associated with cachexia. We undertook studies to determine whether a common histidine (H) to aspartate (D) variant at position 202 in the pro-peptide (position 6 in the mature peptide) interfered with its detection by 3 of the most commonly used immunoassays.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Three synthetic GDF-15-forms (HH homo-, HD hetero-, and DD-homodimers) were measured after serial dilution using Roche Elecsys\u00ae, R&D QuantikineTM ELISA, and MSD R&D DuoSet\u00ae immunoassays. GDF-15 concentrations were measured by the Roche and the MSD R&D immunoassays in 173 genotyped participants (61 HH homozygotes, 59 HD heterozygotes, and 53 DD homozygotes). For the comparative statistical analyses of the GDF-15 concentrations, we used non-parametric tests, in particular Bland\u2013Altman difference (bias) plots and Passing\u2013Bablok regression. The bioactivity of the 2 different homodimers was compared in a cell-based assay in HEK293S-SRF-RET\/GFRAL cells.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The Roche assay detected H- and D-containing peptides similarly but the R&D reagents (Quantikine and DuoSet) consistently underreported GDF-15 concentrations in the presence of the D variant. DD dimers had recoveries of approximately 45% while HD dimers recoveries were 62% to 78%. In human serum samples, the GDF-15 concentrations reported by the R&D assay were a median of 4% lower for HH, a median of 36% lower for HD, and a median of 61% lower for DD compared to the Roche assay. The bioactivities of the HH and DD peptides were indistinguishable.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The D variant of GDF-15 substantially affects its measurement by a commonly used immunoassay, a finding that has clear implications for its interpretation in research and clinical settings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jalm\/jfac055","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T10:47:29Z","timestamp":1657190849000},"page":"1388-1400","source":"Crossref","is-referenced-by-count":38,"title":["The Common H202D Variant in GDF-15 Does Not Affect Its Bioactivity but Can Significantly Interfere with Measurement of Its Circulating Levels"],"prefix":"10.1093","volume":"7","author":[{"given":"Yanislava","family":"Karusheva","sequence":"first","affiliation":[{"name":"MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK"},{"name":"Department of Clinical 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UK"},{"name":"Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust , Cambridge CB2 0QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-8454","authenticated-orcid":false,"given":"Audrey","family":"Melvin","sequence":"additional","affiliation":[{"name":"MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK"},{"name":"Department of Clinical Biochemistry, NIHR Cambridge Biomedical Research Centre , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2593","authenticated-orcid":false,"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Burling","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, NIHR Cambridge Biomedical Research Centre , Cambridge , UK"},{"name":"Department of Biochemistry, University of Cambridge , 80 Tennis Court Road, Cambridge CB2 1GA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Backmark","sequence":"additional","affiliation":[{"name":"Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Roth","sequence":"additional","affiliation":[{"name":"Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Jermutus","sequence":"additional","affiliation":[{"name":"Projects, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Guiu-Jurado","sequence":"additional","affiliation":[{"name":"Department for Clinical Obesity Research, Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Department for Clinical Obesity Research, Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3643","authenticated-orcid":false,"given":"Paul","family":"Welsh","sequence":"additional","affiliation":[{"name":"British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Hyv\u00f6nen","sequence":"additional","affiliation":[{"name":"Biologics Engineering, R&D, AstraZeneca , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2199-4449","authenticated-orcid":false,"given":"Stephen","family":"O\u2019Rahilly","sequence":"additional","affiliation":[{"name":"MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK"},{"name":"Department of Clinical Biochemistry, NIHR Cambridge Biomedical 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