4.7 Article

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes

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SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-019-43793-4

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资金

  1. Academy of Finland [286284, 322098, 285902, 134309, 126925, 121584, 124282, 129378, 117787, 41071, 326420, 310617]
  2. Social Insurance Institution of Finland (Kela)
  3. Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere
  4. Turku University Hospitals [X51001, 9S054]
  5. Juho Vainio Foundation
  6. Paavo Nurmi Foundation
  7. Finnish Foundation for Cardiovascular Research
  8. Finnish Cultural Foundation
  9. Finnish Cultural Foundation - the Pirkanmaa Regional Fund
  10. Tampere Tuberculosis Foundation
  11. Emil Aaltonen Foundation
  12. Yrjo Jahnsson Foundation
  13. Signe and Ane Gyllenberg Foundation
  14. Diabetes Research Foundation of the Finnish Diabetes Association
  15. European Union [201668]
  16. Horizon2020 [755320]
  17. Foundation of Clinical Chemistry
  18. Orion-Farmos Research Foundation
  19. Academy of Finland (AKA) [285902, 310617, 285902, 310617] Funding Source: Academy of Finland (AKA)

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We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n= 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development ofT2D.

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