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Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

Author:
  • Tina Rönn
  • Petr Volkov
  • Linn Gillberg
  • Milana Kokosar
  • Alexander Perfilyev
  • Anna Louisa Jacobsen
  • Sine W Jørgensen
  • Charlotte Brøns
  • Per-Anders Jansson
  • Karl-Fredrik Eriksson
  • Oluf Pedersen
  • Torben Hansen
  • Leif Groop
  • Elisabet Stener-Victorin
  • Allan Vaag
  • Emma A Nilsson
  • Charlotte Ling
Publishing year: 2015
Language: English
Pages: 3792-3813
Publication/Series: Human Molecular Genetics
Volume: 24
Issue: 13
Document type: Journal article
Publisher: Oxford University Press

Abstract english

Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.

Keywords

  • Medical Genetics

Other

Published
  • Diabetes and Endocrinology
  • Epigenetics and Diabetes
  • Clinical Vascular Disease Research
  • ISSN: 0964-6906
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