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 journalArticle (Academic Journal)peer-review

84 Citations (Scopus)


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-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 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.

Original languageEnglish
Pages (from-to)1329-37
Number of pages9
Issue number4
Publication statusPublished - Apr 2013


  • Adolescent
  • Adult
  • Biomarkers
  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus, Type 2
  • Female
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 1-alpha
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Single Nucleotide
  • Polysaccharides
  • Reproducibility of Results
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't


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