PMID- 34944721 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211228 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 9 IP - 12 DP - 2021 Dec 14 TI - Epigenome-Wide Histone Acetylation Changes in Peripheral Blood Mononuclear Cells in Patients with Type 2 Diabetes and Atherosclerotic Disease. LID - 10.3390/biomedicines9121908 [doi] LID - 1908 AB - 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. FAU - Bompada, Pradeep AU - Bompada P AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. FAU - Goncalves, Isabel AU - Goncalves I AUID- ORCID: 0000-0002-2935-0181 AD - Cardiovascular Research-Translational Studies, Institution of Clinical Science Malmo, Lund University, 20502 Malmo, Sweden. AD - Department of Cardiology, Skane University Hospital, 20502 Malmo, Sweden. FAU - Wu, Chuanyan AU - Wu C AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. AD - School of Control Science and Engineering, Shandong University, Jinan 250061, China. AD - School of Intelligent Engineering, Shandong Management University, Jinan 250100, China. FAU - Gao, Rui AU - Gao R AD - School of Control Science and Engineering, Shandong University, Jinan 250061, China. FAU - Sun, Jiangming AU - Sun J AD - Cardiovascular Research-Translational Studies, Institution of Clinical Science Malmo, Lund University, 20502 Malmo, Sweden. FAU - Mir, Bilal Ahmad AU - Mir BA AUID- ORCID: 0000-0002-8194-5991 AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. FAU - Luan, Cheng AU - Luan C AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. FAU - Renstrom, Erik AU - Renstrom E AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. FAU - Groop, Leif AU - Groop L AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. AD - Finnish Institute for Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland. FAU - Weng, Jianping AU - Weng J AD - Clinical Research Hospital, Chinese Academy of Sciences, Hefei 230001, China. AD - Department of Endocrinology and Metabolism, Division of Life Sciences of Medicine, University of Science and Technology of China, Hefei 230001, China. FAU - Hansson, Ola AU - Hansson O AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. AD - Institute for Molecular Medicine Finland (FIMM), Helsinki University, 00290 Helsinki, Finland. FAU - Edsfeldt, Andreas AU - Edsfeldt A AD - Cardiovascular Research-Translational Studies, Institution of Clinical Science Malmo, Lund University, 20502 Malmo, Sweden. AD - Department of Cardiology, Skane University Hospital, 20502 Malmo, Sweden. AD - Wallenberg Center for Molecular Medicine, Lund University, 20502 Malmo, Sweden. FAU - De Marinis, Yang AU - De Marinis Y AUID- ORCID: 0000-0002-8081-2142 AD - Department of Clinical Sciences, Lund University, 20502 Malmo, Sweden. AD - School of Control Science and Engineering, Shandong University, Jinan 250061, China. AD - Clinical Research Hospital, Chinese Academy of Sciences, Hefei 230001, China. AD - Department of Endocrinology and Metabolism, Division of Life Sciences of Medicine, University of Science and Technology of China, Hefei 230001, China. LA - eng GR - 115974/Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974/ GR - JDRF/European Union's Horizon 2020 research and innovation programme and EFPIA with JDRF/ GR - Swedish Research Council/Swedish Research Council/ GR - the Swedish heart and lung foundation/the Swedish heart and lung foundation/ GR - Skane University Hospital grants/Skane University Hospital grants/ GR - Dnr 2009-1039/Strategic Research Area Exodiab/ GR - Dnr IRC15-0067/Swedish Foundation for Strategic Research/ GR - EASD/European Foundation for the Study of Diabetes/ GR - Hjelt Foundation grant/Hjelt Foundation grant/ GR - Pahlsson foundation/Pahlsson foundation/ GR - Exodiab pilot study grant/Exodiab pilot study grant/ GR - the Swedish Society of Medicine/the Swedish Society of Medicine/ GR - The Knut and Alice Wallenberg foundation/The Knut and Alice Wallenberg foundation/ PT - Journal Article DEP - 20211214 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8698994 OTO - NOTNLM OT - ChIP-seq OT - H3K9ac OT - HLA OT - TCF7L2 OT - histone modification OT - type 1 diabetes OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2021/12/25 06:00 MHDA- 2021/12/25 06:01 PMCR- 2021/12/14 CRDT- 2021/12/24 01:06 PHST- 2021/09/29 00:00 [received] PHST- 2021/11/30 00:00 [revised] PHST- 2021/12/06 00:00 [accepted] PHST- 2021/12/24 01:06 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2021/12/25 06:01 [medline] PHST- 2021/12/14 00:00 [pmc-release] AID - biomedicines9121908 [pii] AID - biomedicines-09-01908 [pii] AID - 10.3390/biomedicines9121908 [doi] PST - epublish SO - Biomedicines. 2021 Dec 14;9(12):1908. doi: 10.3390/biomedicines9121908.