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Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes.

Author:
  • Emma A Nilsson
  • Per Anders Jansson
  • Alexander Perfilyev
  • Petr Volkov
  • Maria Pedersen
  • Maria K Svensson
  • Pernille Poulsen
  • Rasmus Ribel-Madsen
  • Nancy L Pedersen
  • Peter Almgren
  • Joao Fadista
  • Tina Rönn
  • Bente Klarlund-Pedersen
  • Camilla Scheele
  • Allan Vaag
  • Charlotte Ling
Publishing year: 2014
Language: English
Pages: 2962-2976
Publication/Series: Diabetes
Volume: 63
Issue: 9
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

Genetics, epigenetics and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from discordant twins, we found decreased expression of genes involved in oxidative phosphorylation, carbohydrate-, amino acid- and lipid metabolism, and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18 and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g. IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2 and IRS1 showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with controls. 1,410 of these sites did also show differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified CNVs in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Endocrinology
  • Epigenetics and Diabetes
  • ISSN: 1939-327X
Tina Rönn
E-mail: tina [dot] ronn [at] med [dot] lu [dot] se

Assistant researcher

Epigenetics and Diabetes

+46 40 39 12 18

CRC 91-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00