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Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes.

Author:
  • Marloes Dekker Nitert
  • Tasnim Dayeh
  • Peter Volkov
  • Targ Elgzyri
  • Elin Hall
  • Emma Nilsson
  • Beatrice Yang
  • Stefan Lang
  • Hemang Parikh
  • Ylva Wessman
  • Holger Weishaupt
  • Joanne Attema
  • Mia Abels
  • Nils Wierup
  • Peter Almgren
  • Per-Anders Jansson
  • Tina Rönn
  • Ola Hansson
  • Karl-Fredrik Eriksson
  • Leif Groop
  • Charlotte Ling
Publishing year: 2012-10-01
Language: English
Publication/Series: Diabetes
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH(+) men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH(+) and FH(-) individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 × 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Endocrinology
  • Epigenetics and Diabetes
  • Neuroendocrine Cell Biology
  • Clinical Vascular Disease Research
  • ISSN: 1939-327X
Tina Rönn
E-mail: tina.ronn [at] med.lu.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