A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




TekijätMononen N, Lyytikainen LP, Seppala I, Mishra PP, Juonala M, Waldenberger M, Klopp N, Illig T, Leiviska J, Loo BM, Laaksonen R, Oksala N, Kahonen M, Hutri-Kahonen N, Raitakari O, Lehtimaki T, Raitoharju E

KustantajaNATURE PUBLISHING GROUP

Julkaisuvuosi2019

JournalScientific Reports

Tietokannassa oleva lehden nimiSCIENTIFIC REPORTS

Lehden akronyymiSCI REP-UK

Artikkelin numero8887

Vuosikerta9

Sivujen määrä14

ISSN2045-2322

eISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-019-43793-4

Verkko-osoitehttps://www.nature.com/articles/s41598-019-43793-4

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/41149940


Tiivistelmä
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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