Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/30064
Title: | The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome | Authors: | REIMANN, Brigitte JANSSEN, Bram ALFANO, Rossella Ghantous, Akram Espin-Perez, Almudena de Koko, Theo M. SAENEN, Nelly COX, Bianca Robinson, Oliver Chadeau-Hyam, Marc PENDERS, Joris Herceg, Zdenko Vineis, Paolo NAWROT, Tim PLUSQUIN, Michelle |
Issue Date: | 2019 | Publisher: | FRONTIERS MEDIA SA | Source: | FRONTIERS IN GENETICS, 10 (Art N° 325) | Abstract: | Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 x 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone modification, CYP-metabolism, and aging, indicating etiological origins in epigenetic programming. Variation in metabolic hormones at birth, reflected by molecular changes, might via these alterations predispose children to metabolic diseases later in life. The results of this study may provide important markers for following targeted studies. | Notes: | [Reimann, Brigitte; Janssen, Bram G.; Alfano, Rossella; Saenen, Nelly D.; Cox, Bianca; Nawrot, Tim S.; Plusquin, Michelle] Univ Hasselt, Ctr Environm Sci, Hasselt, Belgium. [Ghantous, Akram; Herceg, Zdenko] IARC, Epigenet Grp, Lyon, France. [Espin-Perez, Almudena] Stanford Univ, Dept Biomed Informat Res, Stanford, CA 94305 USA. [de Koko, Theo M.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Toxicogen, Maastricht, Netherlands. [Robinson, Oliver; Chadeau-Hyam, Marc; Vineis, Paolo; Plusquin, Michelle] Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England. [Robinson, Oliver; Chadeau-Hyam, Marc; Vineis, Paolo; Plusquin, Michelle] Imperial Coll London, Hlth Protect Agcy Ctr Environm & Hlth, Med Res Council, London, England. [Chadeau-Hyam, Marc] Univ Utrecht, IRAS, Div Environm Epidemiol, Utrecht, Netherlands. [Penders, Joris] East Limburg Hosp, Lab Clin Biol, Genk, Belgium. [Vineis, Paolo] IIGM, Turin, Italy. [Nawrot, Tim S.] Katholieke Univ Leuven, Sch Publ Hlth Occupat & Environm Med, Leuven, Belgium. | Keywords: | insulin;mitochondrial DNA content;epigenome-wide methylation;cord blood insulin levels;mitochondrial dysfunction;differentially methylated regions;DMRs;ENVIRONAGE | Document URI: | http://hdl.handle.net/1942/30064 | e-ISSN: | 1664-8021 | DOI: | 10.3389/fgene.2019.00325 | ISI #: | 000464465100002 | Rights: | 2019 Reimann, Janssen, Alfano, Ghantous, Espín-Pérez, de Kok, Saenen, Cox, Robinson, Chadeau-Hyam, Penders, Herceg, Vineis, Nawrot and Plusquin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
reimann 1.pdf | Published version | 1.4 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
2
checked on Sep 2, 2020
WEB OF SCIENCETM
Citations
6
checked on Oct 13, 2024
Page view(s)
44
checked on Jun 27, 2022
Download(s)
6
checked on Jun 27, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.