You are here

  • Home
  • Archive
  • Volume 8, Issue 1
  • Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: results from the Korea Epigenome Study (KES)

Article Text

Article menu

Download PDFPDF

XML
Obesity studies
Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: results from the Korea Epigenome Study (KES)
  1. In-Uk Koh1,
  2. Nak-Hyeon Choi1,
  3. Kibaick Lee1,
  4. Ho-Yeong Yu1,
  5. Jun Ho Yun1,
  6. Jin-Hwa Kong1,
  7. Hyo Jin Kim2,
  8. Song Lee3,
  9. Song Cheol Kim3,
  10. Bong-Jo Kim1,
  11. Sanghoon Moon1
  1. 1Division of Genome Research, Center for Genome Science, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, South Korea
  2. 2Division of Endocrine and Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, South Korea
  3. 3Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, South Korea
  1. Correspondence to Dr Sanghoon Moon; moon.sanghoon{at}daum.net; Dr Bong-Jo Kim; kbj6181{at}korea.kr

Abstract

Introduction Obesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.

Research design and methods We performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).

Results Seven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.

Conclusions Our finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.

  • obesity
  • cohort
  • inflammation markers
  • metabolism
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2020-001338

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • I-UK and N-HC contributed equally.

    • Contributors I-UK, B-JK, and SM conceptualized and supervised the study. N-HC, KL, and J-HK performed the data analysis and prepared figures and tables. H-YY, JHY, and SL performed experiments. HJK and SCK provided samples and clinical information. I-UK and SM coordinated the research, interpreted the data, searched the literature, and wrote the original draft of manuscript. I-UK, B-JK, and SM reviewed and edited the manuscript. B-JK is the guarantor/supervisor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding This research was supported by intramural grants from the Korea National Institute of Health (2017-NI73002-02 and 2018-NI001-02). Data were provided by Reference Data Production of Regulation of Gene Expression (4848–308) and Korean Genome Analysis Project (4845–301) that were supported by the Korea Centers for Disease Control and Prevention, Republic of Korea.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The Institutional review boards at Korea National Institute of Health approved this study (2017-03-02-2C-A).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request. The deidentified data generated and/or analyzed in this study are available from the Division of Genome Research in Korea National Institute of Health (www.nih.go.kr) on reasonable requests.