Year: 2022
Type: article
Study design: Observational Study
Abstract: 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.
Source: Clinical Epigenetics
Institutions: Universitat de València, Instituto de Salud Carlos III, Columbia University, University of Alabama at Birmingham, Universidad de La Frontera, Texas Biomedical Research Institute, Howard University, Georgetown-Howard Universities Center for Clinical and Translational Science, MedStar Health Research Institute, University of Washington, University of Oklahoma Health Sciences Center, Emory University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,190
Funders: AstraZeneca, “la Caixa” Foundation, Strong, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, Instituto de Salud Carlos III, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences
Awards: G1084631338, Cardiovascular Disease in Sioux Indians, G1168756116, G1232093594, G1241847824, The Strong Heart Study, Phase V, G1565887210, G164614106, CVD in American Indians Biomarker lab and Arizona Field Center, G188800786, G212159931, G2290189609, G2611541099, Strong Heart Family Study, G305513510, G3124311990, G3150909807, Cardiovascular Evaluation for the SHS Phase V, G3191277318, G33163370, G3690828678, G3781439060, G4007245975, Arsenic Exposure, Cardiovascular Disease and Diabetes in Native Americans, G4188254959, CVD in American Indians Genetics Center, G4289235060, G4329341098, CVD in American Indians Study and Data Management Center and OK Field Center, G4944594896, G5132640529, G5252489644, Health Effects and Geochemistry of Arsenic, CVD in American Indians: Imaging and Cardiovascular Center, G6004110409, G6135614585, G6395920388, G65038145, G7245015376, G7309279274, G7380953364, G76056343, G7685134749, CVD in American Indians The Dakota Field Center, G7866934866, G7986252178, G8263684459, Metales y arteriosclerosis subclínica: papel de la variación genética y epigenética en genes candidatos, G8388944883, Arsenic, Epigenetics and Incident Cardiovascular Disease in American Indians, G8565228101, G863538970, G867024095, Arsenic Exposure, Genetic Determinants and Diabetes Risk in a Family Study, G8680181643, G8765877990, G8974218451, Cardiovascular Disease in Pima Indians, The Southwest National Primate Research Center, Columbia University and Northern Plains Partnership for the Superfund Research Program, Center for Environmental Health in Northern Manhattan, G91032504
OpenAlex ID: W4311834560