Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Karl-Fredrik Eriksson

Associate professor

Default user image.

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

Summary, in 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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics
  • Vascular Diseases - Clinical Research
  • EXODIAB: Excellence of Diabetes Research in Sweden

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

Topic

  • Medical Genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics
  • Vascular Diseases - Clinical Research

ISBN/ISSN/Other

  • ISSN: 0964-6906