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Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

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  • Gaya Thanabalasingham
  • Jennifer E Huffman
  • Jayesh J Kattla
  • Mislav Novokmet
  • Anna L Gloyn
  • Barbara Adamczyk
  • Ana Muzinic
  • Neelam Hassanali
  • Maja Pucic
  • Amanda J Bennett
  • Ozren Polasek
  • Saima A Mughal
  • Irma Redzic
  • Dragan Primorac
  • Ivana Kolcic
  • Torben Hansen
  • Daniela Gasperikova
  • Erling Tjora
  • Mark W J Strachan
  • Trine Nielsen
  • Juraj Stanik
  • Iwar Klimes
  • Oluf B Pedersen
  • Pål R Njølstad
  • Ulf Gyllensten
  • Olga Gornik
  • Mark I McCarthy
  • Pauline M Rudd
  • Katharine R Owen
  • Gordan Lauc

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    Rights statement: © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    Final published version, 340 KB, PDF document

    Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Original languageEnglish
Pages (from-to)1329-1337
Issue number4
Early online date28 Dec 2012
Publication statusPublished - Apr 2013


A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-alpha (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-induced MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction.

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