miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222–3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p), our findings suggest a dose-response relationship with impaired fasting glucose and T2D. Two of the six miR-NAs were associated with incident T2D (miR-92b-3p: hazard ratio [HR] 1.64, P = 1.30E-03; miR-222-3p: HR 1.97, P = 9.10E-03) in the highest versus lowest tertile of expression. Most of the T2D-associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic net-work. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.
Bibliographical noteFunding Information:
Acknowledgments. MESA and the MESA SNP Health Association Resource (SHARe) project is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with MESA investigators. Funding. Support for MESA is provided by National Heart, Lung, and Blood Institute grants 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. The MESA Epigenomics and Transcriptomics Studies were funded by National Institutes of Health grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK103531 to J.D. and Y.L. and National Heart, Lung, and Blood Institute grant R01HL119962 to J.S.P. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. D.C.P. researched data and wrote, reviewed, and edited the manuscript. M.W. contributed to the discussion and wrote, reviewed, and edited the manuscript. K.L. performed the statistical analyses. L.H. researched data. A.T.N. contributed to the discussion and reviewed and edited the manuscript. J.D. obtained funding, contributed to the discussion, and reviewed the manuscript. A.B., S.S., G.L.B., D.R.J., and W.P. reviewed the manuscript. D.C. and I.H. researched data and reviewed the manuscript. J.S.P. obtained funding and reviewed the manuscript. Y.L. conceptualized the study, obtained funding, developed the methodology, researched data, and wrote, reviewed, and edited the manuscript. Y.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
© 2022 by the American Diabetes Association.
PubMed: MeSH publication types
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- Research Support, N.I.H., Extramural