Mutations in HNF1A result in marked alterations of plasma glycan profile

Gaya Thanabalasingham, Jennifer E. Huffman, Jayesh J. Kattla, Mislav Novokmet, Igor Rudan, Anna L. Gloyn, Caroline Hayward, Barbara Adamczyk, Rebecca M. Reynolds, Ana Muzinic, Neelam Hassanali, Maja Pucic, Amanda J. Bennett, Abdelkader Essafi, Ozren Polasek, Saima A. Mughal, Irma Redzic, Dragan Primorac, Lina Zgaga, Ivana KolcicTorben Hansen, Daniela Gasperikova, Erling Tjora, Mark W.J. Strachan, Trine Nielsen, Juraj Stanik, Iwar Klimes, Oluf B. Pedersen, Pål R. Njølstad, Sarah H. Wild, Ulf Gyllensten, Olga Gornik, James F. Wilson, Nicholas D. Hastie, Harry Campbell, Mark I. McCarthy, Pauline M. Rudd, Katharine R. Owen, Gordan Lauc, Alan F. Wright

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


A recent genome-wide association study identified hepatocyte nuclear factor 1-a (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-α (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-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1AMODY 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.

Original languageEnglish (US)
Pages (from-to)1329-1337
Number of pages9
Issue number4
StatePublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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