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.

Cheng Luan

Research engineer

Default user image.

Epigenome-Wide Histone Acetylation Changes in Peripheral Blood Mononuclear Cells in Patients with Type 2 Diabetes and Atherosclerotic Disease

Author

  • Pradeep Bompada
  • Isabel Goncalves
  • Chuanyan Wu
  • Rui Gao
  • Jiangming Sun
  • Bilal Ahmad Mir
  • Cheng Luan
  • Erik Renström
  • Leif Groop
  • Jianping Weng
  • Ola Hansson
  • Andreas Edsfeldt
  • Yang De Marinis

Summary, in English

There is emerging evidence of an association between epigenetic modifications, glycemic control and atherosclerosis risk. In this study, we mapped genome-wide epigenetic changes in patients with type 2 diabetes (T2D) and advanced atherosclerotic disease. We performed chromatin immunoprecipitation sequencing (ChIP-seq) using a histone 3 lysine 9 acetylation (H3K9ac) mark in peripheral blood mononuclear cells from patients with atherosclerosis with T2D (n = 8) or without T2D (ND, n = 10). We mapped epigenome changes and identified 23,394 and 13,133 peaks in ND and T2D individuals, respectively. Out of all the peaks, 753 domains near the transcription start site (TSS) were unique to T2D. We found that T2D in atherosclerosis leads to an H3K9ac increase in 118, and loss in 63 genomic regions. Furthermore, we discovered an association between the genomic locations of significant H3K9ac changes with genetic variants identified in previous T2D GWAS. The transcription factor 7-like 2 (TCF7L2) rs7903146, together with several human leukocyte antigen (HLA) variants, were among the domains with the most dramatic changes of H3K9ac enrichments. Pathway analysis revealed multiple activated pathways involved in immunity, including type 1 diabetes. Our results present novel evidence on the interaction between genetics and epigenetics, as well as epigenetic changes related to immunity in patients with T2D and advanced atherosclerotic disease.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Translational Studies
  • Diabetes - Molecular Metabolism
  • Diabetes - Islet Patophysiology
  • WCMM-Wallenberg Centre for Molecular Medicine

Publishing year

2021-12-14

Language

English

Publication/Series

Biomedicines

Volume

9

Issue

12

Document type

Journal article

Publisher

MDPI AG

Topic

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Translational Studies
  • Diabetes - Molecular Metabolism
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 2227-9059