Research Article For reprint orders, please contact: reprints@futuremedicine.com Expression study of candidate miRNAs and evaluation of their potential use as biomarkers of diabetic neuropathy Cinzia Ciccacci* ,1,2 , Andrea Latini 2 , Antonella Colantuono 2 , Cristina Politi 2 , Cinzia D’Amato 3 , Carla Greco 3 , Maria Elena Rinaldi 3 , Davide Lauro 3 , Giuseppe Novelli 2,4 , Vincenza Spallone 3 & Paola Borgiani 2 1 UniCamillus - Saint Camillus International University of Health Sciences, Rome, Italy 2 Department of Biomedicine & Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy 3 Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy 4 IRCCS NEUROMED, Pozzilli, IS, Italy *Author for correspondence: Tel.: +39 06 7259 6090; Fax: +39 06 2042 7313; cinziaciccacci@libero.it Aim: To evaluate the expression of candidate miRNAs in relation to diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). Materials & methods: The expression of six candidate miR- NAs has been evaluated in 49 Type 2 diabetes patients with neurological evaluation. Results: A higher expression of miR-128a was seen in patients with DPN compared with those without DPN (p = 0.015). miR-155 and miR-499a seemed to be down-expressed in patients with DPN (p = 0.04 and p = 0.05, respec- tively). A lower expression of miR-155 (p = 0.05) was observed even in patients with CAN with respect to CAN-negative. A higher expression of miR-155 was associated with the rs767649 polymorphism variant allele compared with the wild-type allele (p = 0.03). Conclusion: miR-128a, miR-155 and miR-499a might be involved in diabetic neuropathies development. First draft submitted: 27 August 2019; Accepted for publication: 5 February 2020; Published online: 13 May 2020 Keywords: diabetic neuropathy • expression study • microRNAs Diabetic neuropathy (DN) is a common complication of diabetes, which affects up to 50% of patients with diabetes [1]. Among the heterogeneous DNs, diabetic distal symmetric sensorimotor polyneuropathy (DPN) and diabetic cardiovascular autonomic neuropathy (CAN) are the most frequent forms, with a prevalence of 30 and 20%, respectively, and both can exert a heavy impact on quality of life, morbidity and mortality [1,2]. The etiopathogenesis of DPN and CAN have not yet been fully understood, but there is a common view that these complications are multifactorial diseases, triggered by the interaction between predisposing genetic, epigenetic and environmental factors. Although hyperglycemia, duration of diabetes, hypertension, dyslipidemia and obesity are recognized as the principal causes of the development of DN, clinical trials have shown that the development of these complications cannot be completely prevented by the control of risk factors, suggesting that genetic factors can play a key role [3]. Indeed, many recent studies have described genetic variations associated with the development of these complications, but only very few genes have been extensively investigated in different populations and confirmed in large cohorts [4]. miRNAs are small (18–22 nucleotides) noncoding RNA molecules, that regulate gene expression at the post- transcriptional level [5] and their alterations may also be involved in the development of various diseases such as cancer, heart, metabolic and inflammatory diseases. In particular, there is increasing evidence of miRNA involvement in development of diabetes and its related complications, including DN [6]. Recently, the association of MIR128A, MIR146A, MIR27A and MIR499A polymorphisms with the risk of developing DNs in an Italian cohort of patients with Type 2 diabetes (T2D) has been described [7,8]. The T allele of rs11888095 single nucleotide polymorphism (SNP) in MIR128A was significantly more frequent in T2D patients with DPN and correlated with a higher DPN severity. The variant allele of rs2910164 SNP in MIR146A seemed to have a protective role for both DPN and CAN. Conversely, the variant allele of rs895819 SNP in MIR27A resulted Epigenomics (Epub ahead of print) ISSN 1750-1911 10.2217/epi-2019-0242 C  2020 Future Medicine Ltd