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

Clinical Epigenetics

Research

Ying Zhang¹  Maria Tellez-Plaza²  Arce Domingo-Relloso³  Ana Navas-Acien⁴  Amanda M. Fretts⁵  Matthew O. Gribble⁶  M. Daniele Fallin⁷  Todd M. Everson⁸  Jason G. Umans⁹  Angela L. Riffo-Campos^1,10  Shelley A. Cole^1,11  Karin Haack^1,11 

[1] Department of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain;Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain;Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA;Department of Statistics and Operations Research, University of Valencia, Valencia, Spain;Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA;Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA;Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA;Emory University Rollins School of Public Health, Atlanta, GA, USA;Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA;Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA;Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA;MedStar Health Research Institute, Hyattsville, MD, USA;Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA;Millennium Nucleus On Sociomedicine (SocioMed) and Vicerrectoría Académica, Universidad de La Frontera, Temuco, Chile;Department of Computer Science, ETSE, University of Valencia, Valencia, Spain;Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA;

关键词: Epigenetics;    Type 2 diabetes;    DNA methylation;    American Indians;   

DOI  :  10.1186/s13148-022-01392-7

 received in 2022-10-27, accepted in 2022-11-30,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsAmong 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.)ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2022

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