P1540: STUDY OF MIRNA EXPRESSION PROFILES IN GAUCHER PATIENTS AND THEIR RELATIONSHIP WITH THE SEVERITY OF BONE INVOLVEMENT

Abstract

Background: Bone manifestations are one of the most prevalent comorbidities in Gaucher disease (GD) and, compromise the quality of life. They are evaluated by DEXA and MRI and several scores are available to assess its severity. Nowadays, no good biomarkers are available for this complication. miRNA are small non-coding RNA molecules whose function is regulate gene expression, and several of them were related to bone disease. Aims: Identify different miRNA expression patterns, depending on the severity of bone involvement in patients with GD and, evaluate its predictive value. Methods: 60 GD naïve patients, were selected and classified according to their bone disease severity using the S-MRI score, considering mild bone disease (MiBD; S-MRI<5), moderate (MoBD; S-MRI: 5-11) and, severe (SBD; S-MRI>11). miRNA was obtained from plasmatic exosomes using miRCURY Exosome Serum/Plasma and miRNeasy Serum/Plasma Advanced kits (QIAGEN) following manufacturer instructions. NGS technology and principal component analysis, corrected by sex and age, were applied to determine miRNA expression profiles. Results: Patients were distributed proportionally in each group (20-20-20), gender distribution was equal between groups, and age was [median (Q1-Q3)]: 19.0 (4.00-40.00) – 40.5 (28.25-56.00) – 37.5 (31.25-47.00) years for MiBD, MoBD and SBD respectively. When compared MiBD against MoBD 3 miRNA were downexpressed in the MoDB group meanwhile 1 was increased. When MiBS vs SBD were compared 4 miRNA were downregulated and 5 increased on the SBD group. Only one miRNA is upregulated on MoDB and even more so in the SBD. Summary/Conclusion: One miRNA, related inversely with osteoblastic differentiation is increased according with the bone severity. So, those preliminary results show an altered miRNA expression depending on the bone severity. Nowadays, we are validating them and trying to predict target-genes and the biological pathway they are involve. Disclosure: Project founded by a Sanofi’s grant (SGZ-2019-12810).