Abstract

Type 2 diabetes and obesity are well-studied metabolic diseases, which are based on genetic and epigenetic alterations in combination with an obesogenic lifestyle. The aim of this study was to test whether SNPs in miRNA-mRNA binding sites that potentially disrupt binding, elevate the expression of miRNA targets, which participate in the development of metabolic diseases. A computational approach was developed that integrates transcriptomics, linkage analysis, miRNA-target prediction data, and sequence information of a mouse model of obesity and diabetes. A statistical analysis demonstrated a significant enrichment of 566 genes for a location in obesity- and diabetes-related QTL. They are expressed at higher levels in metabolically relevant tissues presumably due to altered miRNA-mRNA binding sites. Of these, 51 genes harbor conserved and impaired miRNA-mRNA-interactions in human. Among these, 38 genes have been associated to metabolic diseases according to the phenotypes of corresponding knockout mice or other results described in the literature. The remaining 13 genes (e.g. Jrk, Megf9, Slfn8 and Tmem132e) could be interesting candidates and will be investigated in the future.

Details

Title
Polymorphisms in miRNA binding sites involved in metabolic diseases in mice and humans
Author
Gottmann Pascal 1 ; Ouni Meriem 1 ; Zellner, Lisa 1 ; Jähnert Markus 1 ; Rittig Kilian 2 ; Walther, Dirk 3 ; Schürmann, Annette 4 

 German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, Nuthetal, Germany (GRID:grid.418213.d) (ISNI:0000 0004 0390 0098); German Center for Diabetes Research (DZD), München, Germany (GRID:grid.452622.5) 
 Clinic for Angiology and Diabetology, Frankfurt (Oder), Germany (GRID:grid.452622.5); University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany (GRID:grid.11348.3f) (ISNI:0000 0001 0942 1117) 
 Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, Potsdam, Germany (GRID:grid.418390.7) (ISNI:0000 0004 0491 976X) 
 German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, Nuthetal, Germany (GRID:grid.418213.d) (ISNI:0000 0004 0390 0098); German Center for Diabetes Research (DZD), München, Germany (GRID:grid.452622.5); University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany (GRID:grid.11348.3f) (ISNI:0000 0001 0942 1117); Faculty of Health Sciences, joint Faculty of the Brandenburg University of Technology Cottbus – Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Potsdam, Germany (GRID:grid.11348.3f) (ISNI:0000 0001 0942 1117) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2396289002
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.