Interlaboratory evaluation of plasma N-glycan antennary fucosylation as a clinical biomarker for HNF1A-MODY using liquid chromatography methods

Antennary fucosylation alterations in plasma glycoproteins have been previously proposed and tested as a biomarker for differentiation of maturity onset diabetes of the young (MODY) patients carrying a functional mutation in the HNF1A gene. Here, we developed a novel LC-based workflow to analyze blo...

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Bibliographic Details
Published in:Glycoconjugate journal 2021-06, Vol.38 (3), p.375-386
Main Authors: Demus, Daniel, Jansen, Bas C., Gardner, Richard A., Urbanowicz, Paulina A., Wu, Haiyang, Štambuk, Tamara, Juszczak, Agata, Medvidović, Edita Pape, Juge, Nathalie, Gornik, Olga, Owen, Katharine R., Spencer, Daniel I. R.
Format: Article
Language:English
Subjects:
Adult
Biochemistry
Biomarkers
Biomedical and Life Sciences
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Female
Gene Expression Regulation
Glycoproteins
Hepatocyte Nuclear Factor 1-alpha - genetics
Hepatocyte Nuclear Factor 1-alpha - metabolism
HNF1a gene
Humans
Laboratories
Life Sciences
Liquid chromatography
Male
Mutation
Observer Variation
Original
Original Article
Pathology
Polysaccharides - blood
Polysaccharides - chemistry
Polysaccharides - metabolism
Young Adult
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Summary:Antennary fucosylation alterations in plasma glycoproteins have been previously proposed and tested as a biomarker for differentiation of maturity onset diabetes of the young (MODY) patients carrying a functional mutation in the HNF1A gene. Here, we developed a novel LC-based workflow to analyze blood plasma N-glycan fucosylation in 320 diabetes cases with clinical features matching those at risk of HNF1A-MODY. Fucosylation levels measured in two independent research centers by using similar LC-based methods were correlated to evaluate the interlaboratory performance of the biomarker. The interlaboratory study showed good correlation between fucosylation levels measured for the 320 cases in the two centers with the correlation coefficient (r) of up to 0.88 for a single trait A3FG3S2. The improved chromatographic separation allowed the identification of six single glycan traits and a derived antennary fucosylation trait that were able to differentiate individuals carrying pathogenic mutations from benign or no HNF1A mutation cases, as determined by the area under the curve (AUC) of up to 0.94. The excellent (r = 0.88) interlaboratory performance of the glycan biomarker for HNF1A-MODY further supports the development of a clinically relevant diagnostic test measuring antennary fucosylation levels.
ISSN:0282-0080
1573-4986
1573-4986
DOI:10.1007/s10719-021-09992-w