The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes
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ORIGINAL ARTICLE
The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes Massimo Porta 1 Cristina Amione1 Federica Barutta1 Paolo Fornengo1 Stefano Merlo1 Gabriella Gruden1 Luigi Albano2 Marco Ciccarelli2 Paola Ungaro2 Marilena Durazzo1 Francesco Beguinot2,3 Paola Berchialla4 Franco Cavallo5 Marina Trento1 ●
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Received: 6 May 2018 / Accepted: 23 August 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract Purpose We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes. Methods Cross-sectional, case–control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables. Results Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, GCSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any. Conclusions Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated. Keywords Type 2 diabetes Histone methylation Epigenetics CARM1 ●
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Abbreviations CARM1 Co-activator-associated aRginine Methyltransferase 1 FGF Fibroblast growth factor G-CSF Granulocyte colony-stimulating factor GIP Gastric inhibitory polypeptide or glucosedependent insulinotropic peptide GLP-1 Glucagon-like peptide 1 IFN-γ Interferon gamma IP-10 Interferon-γ-inducible protein 10 IL-1ra Interleukin-1 receptor antagonist
IL-1β IL-4 IL-5 IL-6 IL-7 IL-9 IL-10 IL-12 IL-13 IL-17 MCP-1
* Massimo Porta [email protected]
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Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
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Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
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Department of Public Health and Paediatric Sciences, University of Turin, Turin, Italy
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Department of Medical Sciences, Laboratory of Clinical Pedagogy, University of Turin, Turin, Italy
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National Research Council, URT of the Institute of Experimental Endocrinology Oncology “G. Salvatore”, Naples, Italy
InterLeukin 1 beta InterLeukin 4 I
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