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Sci Rep. 2019 Jun 20;9(1):8887. doi: 10.1038/s41598-019-43793-4.

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

Author information

1
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
2
Division of Medicine, Turku University Hospital, and Department of Medicine, University of Turku, Turku, Finland.
3
Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.
4
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
5
Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
6
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital HUSLAB, Helsinki, Finland.
7
Joint Clinical Biochemistry Laboratory of the University of Turku and Turku University Central Hospital and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
8
Centre for Vascular Surgery and Interventional Radiology, Tampere University Hospital, Tampere, Finland.
9
Department of Clinical Physiology, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
10
Department of Pediatrics, Tampere University and Tampere University Hospital, Tampere, Finland.
11
Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
12
Department of Clinical Physiology and Nuclear Medicine and Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
13
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. emma.raitoharju@uta.fi.

Abstract

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 of T2D.

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