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  3. Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study

  • Front Endocrinol (Lausanne). 2022 Oct 10:13:934706. doi: 10.3389/fendo.2022.934706.
Prasoon Agarwal 1 2,  Brandy A Wicklow 1 3,  Allison B Dart 1 3,  Nikho A Hizon 1 4,  Elizabeth A C Sellers 1 3,  Jonathan M McGavock 1 3,  Charlotte P J Talbot 1 2,  Mario A Fonseca 1 2,  Wayne Xu 4 5,  James R Davie 1 4 5,  Meaghan J Jones 1 4,  Animesh Acharjee 6 7 8,  Vernon W Dolinsky 1 2
Affiliations

Affiliations

  • 1 Diabetes Research Envisioned and Accomplished in Manitoba (DREAM), Research Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
  • 2 Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada.
  • 3 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
  • 4 Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
  • 5 Research Institute in Oncology and Hematology, University of Manitoba, Winnipeg, MB, Canada.
  • 6 Institute of Cancer and Genomic Sciences, University of Birmingham, Winnipeg, MB, Canada.
  • 7 Institute of Translational Medicine, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom.
  • 8 National Institute for Health and Care Research (NIHR) Surgical Reconstruction and Microbiology Research Centre, Birmingham, United Kingdom.
PMID: 36303872 DOI: 10.3389/fendo.2022.934706
Abstract

Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.

Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.

Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in Metabolic Disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among Others.

Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

Keywords

DNA methylation; integration of data; metabolomics; pediatrics; type 2 diabetes mellitus.

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