Frontiers in Endocrinology (Oct 2022)
Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study
- Prasoon Agarwal,
- Prasoon Agarwal,
- Brandy A. Wicklow,
- Brandy A. Wicklow,
- Allison B. Dart,
- Allison B. Dart,
- Nikho A. Hizon,
- Nikho A. Hizon,
- Elizabeth A.C. Sellers,
- Elizabeth A.C. Sellers,
- Jonathan M. McGavock,
- Jonathan M. McGavock,
- Charlotte P. J. Talbot,
- Charlotte P. J. Talbot,
- Mario A. Fonseca,
- Mario A. Fonseca,
- Wayne Xu,
- Wayne Xu,
- James R. Davie,
- James R. Davie,
- James R. Davie,
- Meaghan J. Jones,
- Meaghan J. Jones,
- Animesh Acharjee,
- Animesh Acharjee,
- Animesh Acharjee,
- Vernon W. Dolinsky,
- Vernon W. Dolinsky
Affiliations
- Prasoon Agarwal
- 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
- Prasoon Agarwal
- Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
- Brandy A. Wicklow
- 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
- Brandy A. Wicklow
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
- Allison B. Dart
- 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
- Allison B. Dart
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
- Nikho A. Hizon
- 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
- Nikho A. Hizon
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada
- Elizabeth A.C. Sellers
- 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
- Elizabeth A.C. Sellers
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
- Jonathan M. McGavock
- 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
- Jonathan M. McGavock
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
- Charlotte P. J. Talbot
- 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
- Charlotte P. J. Talbot
- Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
- Mario A. Fonseca
- 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
- Mario A. Fonseca
- Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
- Wayne Xu
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada
- Wayne Xu
- Research Institute in Oncology and Hematology, University of Manitoba, Winnipeg, MB, Canada
- James R. Davie
- 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
- James R. Davie
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada
- James R. Davie
- Research Institute in Oncology and Hematology, University of Manitoba, Winnipeg, MB, Canada
- Meaghan J. Jones
- 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
- Meaghan J. Jones
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada
- Animesh Acharjee
- Institute of Cancer and Genomic Sciences, University of Birmingham, Winnipeg, MB, Canada
- Animesh Acharjee
- Institute of Translational Medicine, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
- Animesh Acharjee
- National Institute for Health and Care Research (NIHR) Surgical Reconstruction and Microbiology Research Centre, Birmingham, United Kingdom
- Vernon W. Dolinsky
- 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
- Vernon W. Dolinsky
- Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
- DOI
- https://doi.org/10.3389/fendo.2022.934706
- Journal volume & issue
-
Vol. 13
Abstract
ObjectiveRates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.MethodsWe 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.ResultsOur 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.ConclusionsWe 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.
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