Epimutation analysis reveals involvement of SLIT2/ROBO signaling pathway in painful diabetic neuropathy
Changes in gene function or expression caused by epigenetic modifications may play a role in painful diabetic neuropathy. Two independent cohorts of patients deeply phenotyped for painful diabetic neuropathy underwent whole genome DNA methylation data analysis. Burden of rare site events at the global, chromosomal and gene level; epigenetic homogeneity for regions enriched in epivariants (epilesions) and functional analysis of the genes with stochastic phenomena was undertaken. This revealed significant involvement of the SLIT/ROBO signaling axis-engaged in peripheral nerve regeneration after injury, among several molecular pathways, making it an attractive therapeutic target in patients with diabetic painful neuropathy.
Authors
- Katarzyna Malgorzata Kwiatkowska (ORCID: https://orcid.org/0000-0002-1536-5024)
- DAN ZIEGLER
- Gastone Castellani (ORCID: https://orcid.org/0000-0003-4892-925X)
- Rayaz Ahmed Malik (ORCID: https://orcid.org/0000-0002-7188-8903)
- Massimiliano Bonafè (ORCID: https://orcid.org/0000-0002-5218-6551)
- Maria Giulia Bacalini (ORCID: https://orcid.org/0000-0003-1618-2673)
- Claudia Sala (ORCID: https://orcid.org/0000-0003-4031-4648)
- Csilla I. Szabo (ORCID: https://orcid.org/0000-0002-6125-7948)
- Luciano Calzari (ORCID: https://orcid.org/0000-0003-4283-0988)
- Salvi Erika
- Chiara Pirazzini
- Paolo Garagnani
- Margherita Marchi
- Giuseppe Lauria
- Davide Gentilini
- Francesca Ferraresi
- Catharina G. Faber
Institutions
- University of Milan (IT)
- University of Pavia (IT)
- Manchester Academic Health Science Centre (GB)
- Maastricht University Medical Centre (NL)
- Manchester University NHS Foundation Trust (GB)
- Azienda USL di Bologna (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Weill Cornell Medical College in Qatar (QA)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Heinrich Heine University Düsseldorf (DE)
- University of Bologna (IT)
Publication Details
- Journal
- Human Genomics
- Published
- 2026-01-09
- DOI
- https://doi.org/10.1186/s40246-025-00905-8
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00