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Demus D, Urbanowicz PA, Gardner RA, et al. Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY. Glycobiology. 2021;doi: 10.1093/glycob/cwab107.
Demus, D., Urbanowicz, P. A., Gardner, R. A., Wu, H., Juszczak, A., Štambuk, T., Medvidović, E. P., Owen, K. R., Gornik, O., Juge, N., & Spencer, D. I. R. (2021). Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY. Glycobiology, . https://doi.org/10.1093/glycob/cwab107
Demus, Daniel, et al. "Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY." Glycobiology vol. (2021). doi: https://doi.org/10.1093/glycob/cwab107
Demus D, Urbanowicz PA, Gardner RA, Wu H, Juszczak A, Štambuk T, Medvidović EP, Owen KR, Gornik O, Juge N, Spencer DIR. Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY. Glycobiology. 2021 Oct 25; doi: 10.1093/glycob/cwab107. Epub 2021 Oct 25. PMID: 34939081.
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Glycobiology. 2021 Oct 25; doi: 10.1093/glycob/cwab107. Epub 2021 Oct 25.

Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY.

Glycobiology

Daniel Demus, Paulina A Urbanowicz, Richard A Gardner, Haiyang Wu, Agata Juszczak, Tamara Štambuk, Edita Pape Medvidović, Katharine R Owen, Olga Gornik, Nathalie Juge, Daniel I R Spencer

Affiliations

  1. Ludger Ltd., Culham Science Centre, Abingdon, OX14 3EB, United Kingdom.
  2. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
  3. The Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom.
  4. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, United Kingdom.
  5. Genos Glycoscience Research Laboratory, Borongajska cesta 83h, 10000, Zagreb, Croatia.
  6. Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kova?i?a 1, 10000 Zagreb, Croatia.
  7. Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb University School of Medicine, Dugi dol 4A, 10000, Zagreb, Croatia.
  8. NIHR Oxford Biomedical Research Centre, Oxford Hospitals NHS Foundation Trust, Oxford, OX3 9DU, United Kingdom.

PMID: 34939081 DOI: 10.1093/glycob/cwab107

Abstract

Maturity-onset diabetes of the young due to hepatocyte nuclear factor-1 alpha variants (HNF1A-MODY) causes monogenic diabetes. Individuals carrying damaging variants in HNF1A show decreased levels of α1-3,4 fucosylation, as demonstrated on antennary fucosylation of blood plasma N-glycans. The excellent diagnostic performance of this glycan biomarker in blood plasma N-glycans of individuals with HNF1A-MODY has been demonstrated using liquid chromatography methods. Here, we have developed a high-throughput exoglycosidase plate-based assay to measure α1-3,4 fucosylation levels in blood plasma samples. The assay has been optimized and its validity tested using 1000 clinical samples from a cohort of individuals with young-adult onset diabetes including cases with HNF1A-MODY. The α1-3,4 fucosylation levels in blood plasma showed a good differentiating power in identifying cases with damaging HNF1A variants, as demonstrated by receiver operating characteristic curve analysis with the AUC values of 0.87 and 0.95. This study supports future development of a simple diagnostic test to measure this glycan biomarker for application in a clinical setting.

© The Author(s) 2021. Published by Oxford University Press.

Keywords: biomarker; diabetes; fucosylation; glycans; hnf1a-mody

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