Mutations in HNF1A result in marked alterations of plasma glycan profile
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Mutations in HNF1A result in marked alterations of plasma glycan profile. / Thanabalasingham, Gaya; Huffman, Jennifer E; Kattla, Jayesh J; Novokmet, Mislav; Rudan, Igor; Gloyn, Anna L; Hayward, Caroline; Adamczyk, Barbara; Reynolds, Rebecca M; Muzinic, Ana; Hassanali, Neelam; Pucic, Maja; Bennett, Amanda J; Essafi, Abdelkader; Polasek, Ozren; Mughal, Saima A; Redzic, Irma; Primorac, Dragan; Zgaga, Lina; Kolcic, Ivana; Hansen, Torben; Gasperikova, Daniela; Tjora, Erling; Strachan, Mark W J; Nielsen, Trine; Stanik, Juraj; Klimes, Iwar; Pedersen, Oluf B; Njølstad, Pål R; Wild, Sarah H; Gyllensten, Ulf; Gornik, Olga; Wilson, James F; Hastie, Nicholas D; Campbell, Harry; McCarthy, Mark I; Rudd, Pauline M; Owen, Katharine R; Lauc, Gordan; Wright, Alan F.
In: Diabetes, Vol. 62, No. 4, 04.2013, p. 1329-37.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Mutations in HNF1A result in marked alterations of plasma glycan profile
AU - Thanabalasingham, Gaya
AU - Huffman, Jennifer E
AU - Kattla, Jayesh J
AU - Novokmet, Mislav
AU - Rudan, Igor
AU - Gloyn, Anna L
AU - Hayward, Caroline
AU - Adamczyk, Barbara
AU - Reynolds, Rebecca M
AU - Muzinic, Ana
AU - Hassanali, Neelam
AU - Pucic, Maja
AU - Bennett, Amanda J
AU - Essafi, Abdelkader
AU - Polasek, Ozren
AU - Mughal, Saima A
AU - Redzic, Irma
AU - Primorac, Dragan
AU - Zgaga, Lina
AU - Kolcic, Ivana
AU - Hansen, Torben
AU - Gasperikova, Daniela
AU - Tjora, Erling
AU - Strachan, Mark W J
AU - Nielsen, Trine
AU - Stanik, Juraj
AU - Klimes, Iwar
AU - Pedersen, Oluf B
AU - Njølstad, Pål R
AU - Wild, Sarah H
AU - Gyllensten, Ulf
AU - Gornik, Olga
AU - Wilson, James F
AU - Hastie, Nicholas D
AU - Campbell, Harry
AU - McCarthy, Mark I
AU - Rudd, Pauline M
AU - Owen, Katharine R
AU - Lauc, Gordan
AU - Wright, Alan F
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Biological Markers
KW - Diabetes Mellitus, Type 1
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Gene Expression Regulation
KW - Hepatocyte Nuclear Factor 1-alpha
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation, Missense
KW - Polymorphism, Single Nucleotide
KW - Polysaccharides
KW - Reproducibility of Results
KW - Young Adult
U2 - 10.2337/db12-0880
DO - 10.2337/db12-0880
M3 - Journal article
C2 - 23274891
VL - 62
SP - 1329
EP - 1337
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 48873588