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Tina Rönn

Tina Rönn

Assistant researcher

Tina Rönn

Epigenetic changes in islets of langerhans preceding the onset of diabetes

Author

  • Meriem Ouni
  • Sophie Saussenthaler
  • Fabian Eichelmann
  • Markus Jähnert
  • Mandy Stadion
  • Clemens Wittenbecher
  • Tina Rönn
  • Lisa Zellner
  • Pascal Gottmann
  • Charlotte Ling
  • Matthias B. Schulze
  • Annette Schürmann

Summary, in English

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for pre-vention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2020

Language

English

Pages

2503-2517

Publication/Series

Diabetes

Volume

69

Issue

11

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes
  • Medical Genetics

Status

Published

Research group

  • Diabetes - Epigenetics

ISBN/ISSN/Other

  • ISSN: 0012-1797