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Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study

BACKGROUND: The prevalence of type 2 diabetes has dramatically increased in the past years. Increasing evidence supports that blood DNA methylation, the best studied epigenetic mark, is related to diabetes risk. Few prospective studies, however, are available. We studied the association of blood DNA...

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Autores principales: Domingo-Relloso, Arce, Gribble, Matthew O., Riffo-Campos, Angela L., Haack, Karin, Cole, Shelley A., Tellez-Plaza, Maria, Umans, Jason G., Fretts, Amanda M., Zhang, Ying, Fallin, M. Daniele, Navas-Acien, Ana, Everson, Todd M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759920/
https://www.ncbi.nlm.nih.gov/pubmed/36529747
http://dx.doi.org/10.1186/s13148-022-01392-7
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author Domingo-Relloso, Arce
Gribble, Matthew O.
Riffo-Campos, Angela L.
Haack, Karin
Cole, Shelley A.
Tellez-Plaza, Maria
Umans, Jason G.
Fretts, Amanda M.
Zhang, Ying
Fallin, M. Daniele
Navas-Acien, Ana
Everson, Todd M.
author_facet Domingo-Relloso, Arce
Gribble, Matthew O.
Riffo-Campos, Angela L.
Haack, Karin
Cole, Shelley A.
Tellez-Plaza, Maria
Umans, Jason G.
Fretts, Amanda M.
Zhang, Ying
Fallin, M. Daniele
Navas-Acien, Ana
Everson, Todd M.
author_sort Domingo-Relloso, Arce
collection PubMed
description BACKGROUND: The prevalence of type 2 diabetes has dramatically increased in the past years. Increasing evidence supports that blood DNA methylation, the best studied epigenetic mark, is related to diabetes risk. Few prospective studies, however, are available. We studied the association of blood DNA methylation with diabetes in the Strong Heart Study. We used limma, Iterative Sure Independence Screening and Cox regression to study the association of blood DNA methylation with fasting glucose, HOMA-IR and incident type 2 diabetes among 1312 American Indians from the Strong Heart Study. DNA methylation was measured using Illumina’s MethylationEPIC beadchip. We also assessed the biological relevance of our findings using bioinformatics analyses. RESULTS: Among the 358 differentially methylated positions (DMPs) that were cross-sectionally associated either with fasting glucose or HOMA-IR, 49 were prospectively associated with incident type 2 diabetes, although no DMPs remained significant after multiple comparisons correction. Multiple of the top DMPs were annotated to genes with relevant functions for diabetes including SREBF1, associated with obesity, type 2 diabetes and insulin sensitivity; ABCG1, involved in cholesterol and phospholipids transport; and HDAC1, of the HDAC family. (HDAC inhibitors have been proposed as an emerging treatment for diabetes and its complications.) CONCLUSIONS: Our results suggest that differences in peripheral blood DNA methylation are related to cross-sectional markers of glucose metabolism and insulin activity. While some of these DMPs were modestly associated with prospective incident type 2 diabetes, they did not survive multiple testing. Common DMPs with diabetes epigenome-wide association studies from other populations suggest a partially common epigenomic signature of glucose and insulin activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01392-7.
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spelling pubmed-97599202022-12-19 Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study Domingo-Relloso, Arce Gribble, Matthew O. Riffo-Campos, Angela L. Haack, Karin Cole, Shelley A. Tellez-Plaza, Maria Umans, Jason G. Fretts, Amanda M. Zhang, Ying Fallin, M. Daniele Navas-Acien, Ana Everson, Todd M. Clin Epigenetics Research BACKGROUND: The prevalence of type 2 diabetes has dramatically increased in the past years. Increasing evidence supports that blood DNA methylation, the best studied epigenetic mark, is related to diabetes risk. Few prospective studies, however, are available. We studied the association of blood DNA methylation with diabetes in the Strong Heart Study. We used limma, Iterative Sure Independence Screening and Cox regression to study the association of blood DNA methylation with fasting glucose, HOMA-IR and incident type 2 diabetes among 1312 American Indians from the Strong Heart Study. DNA methylation was measured using Illumina’s MethylationEPIC beadchip. We also assessed the biological relevance of our findings using bioinformatics analyses. RESULTS: Among the 358 differentially methylated positions (DMPs) that were cross-sectionally associated either with fasting glucose or HOMA-IR, 49 were prospectively associated with incident type 2 diabetes, although no DMPs remained significant after multiple comparisons correction. Multiple of the top DMPs were annotated to genes with relevant functions for diabetes including SREBF1, associated with obesity, type 2 diabetes and insulin sensitivity; ABCG1, involved in cholesterol and phospholipids transport; and HDAC1, of the HDAC family. (HDAC inhibitors have been proposed as an emerging treatment for diabetes and its complications.) CONCLUSIONS: Our results suggest that differences in peripheral blood DNA methylation are related to cross-sectional markers of glucose metabolism and insulin activity. While some of these DMPs were modestly associated with prospective incident type 2 diabetes, they did not survive multiple testing. Common DMPs with diabetes epigenome-wide association studies from other populations suggest a partially common epigenomic signature of glucose and insulin activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01392-7. BioMed Central 2022-12-18 /pmc/articles/PMC9759920/ /pubmed/36529747 http://dx.doi.org/10.1186/s13148-022-01392-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Domingo-Relloso, Arce
Gribble, Matthew O.
Riffo-Campos, Angela L.
Haack, Karin
Cole, Shelley A.
Tellez-Plaza, Maria
Umans, Jason G.
Fretts, Amanda M.
Zhang, Ying
Fallin, M. Daniele
Navas-Acien, Ana
Everson, Todd M.
Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title_full Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title_fullStr Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title_full_unstemmed Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title_short Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study
title_sort epigenetics of type 2 diabetes and diabetes-related outcomes in the strong heart study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759920/
https://www.ncbi.nlm.nih.gov/pubmed/36529747
http://dx.doi.org/10.1186/s13148-022-01392-7
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