Fucosylated AGP glycopeptides as biomarkers of HNF1A-Maturity onset diabetes of the young

Tijardović, Marko; Štambuk, Tamara; Juszczak, Agata; Keser, Toma; Gasperikova, Daniela; Novokmet, Mislav; Tjora, Erling; Pape Medvidović, Edita; Stanik, Juraj; Rasmus Njølstad, Pål; Lauc, Gordan; Owen, Katharine R.; Gornik, Olga

doi:10.1016/j.diabres.2022.109226

Pregled bibliografske jedinice broj: 1178944

Fucosylated AGP glycopeptides as biomarkers of HNF1A-Maturity onset diabetes of the young

Tijardović, Marko; Štambuk, Tamara; Juszczak, Agata; Keser, Toma; Gasperikova, Daniela; Novokmet, Mislav; Tjora, Erling; Pape Medvidović, Edita; Stanik, Juraj; Rasmus Njølstad, Pål et al.

Fucosylated AGP glycopeptides as biomarkers of HNF1A-Maturity onset diabetes of the young // Diabetes Research and Clinical Practice, 185 (2022), 109226, 8 doi:10.1016/j.diabres.2022.109226 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 1178944 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Fucosylated AGP glycopeptides as biomarkers of HNF1A-Maturity onset diabetes of the young

Autori
Tijardović, Marko ; Štambuk, Tamara ; Juszczak, Agata ; Keser, Toma ; Gasperikova, Daniela ; Novokmet, Mislav ; Tjora, Erling ; Pape Medvidović, Edita ; Stanik, Juraj ; Rasmus Njølstad, Pål ; Lauc, Gordan ; Owen, Katharine R. ; Gornik, Olga

Izvornik
Diabetes Research and Clinical Practice (0168-8227) 185 (2022); 109226, 8

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
MODY ; Type 2 diabetes mellitus ; Alpha-1-acid glycoprotein ; N-glycosylation ; Glycoprotein ; LC-MS

Sažetak
Aims We previously demonstrated that antennary fucosylated N-glycans on plasma proteins are regulated by HNF1A and can identify cases of Maturity-Onset Diabetes of the Young caused by HNF1A variants (HNF1A-MODY). Based on literature data, we further postulated that N-glycans with best diagnostic value mostly originate from alpha- 1-acid glycoprotein (AGP). In this study we analyzed fucosylation of AGP in subjects with HNF1A- MODY and other types of diabetes aiming to evaluate its diagnostic potential. Methods A recently developed LC-MS method for AGP N- glycopeptide analysis was utilized in two independent cohorts: a) 466 subjects with different diabetes subtypes to test the fucosylation differences, b) 98 selected individuals to test the discriminative potential for pathogenic HNF1A variants. Results Our results showed significant reduction in AGP fucosylation associated to HNF1A-MODY when compared to other diabetes subtypes. Additionally, ROC curve analysis confirmed significant discriminatory potential of individual fucosylated AGP glycopeptides, where the best performing glycopeptide had an AUC of 0.94 (95% CI 0.90– 0.99). Conclusions A glycopeptide based diagnostic tool would be beneficial for patient stratification by providing information about the functionality of HNF1A. It could assist the interpretation of DNA sequencing results and be a useful addition to the differential diagnostic process.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA

Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb,
Klinika za dijabetes, endokrinologiju i bolesti metabolizma Vuk Vrhovac,
Medicinski fakultet, Zagreb,
GENOS d.o.o.

Profili:

Tamara Štambuk (autor)