Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in patients with type 2 diabetes

Maguelonne Roux (1) , Claire Perret (1) , Eva Feigerlova (2, 3, 4, 5) , Badreddine Mohand Oumoussa (6) , Pierre-Jean Saulnier (2, 3, 4, 5) , Carole Proust (1) , David-Alexandre Trégouët (1) , Samy Hadjadj (2, 3, 4, 5)

1 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
2 Service Endocrinologie [CHU Poitiers]
3 IRTOMIT - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques
4 Université de Poitiers - Faculté de Médecine et de Pharmacie
5 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
6 P3S - Plateforme Post-génomique de la Pitié-Salpêtrière

Background: MicroRNAs (miRNAs) are small non-coding RNAs participating in post-transcriptional regulation of genes. Their key role in modulating the susceptibility to human diseases is now widely recognized, in particular in the context of cardiometabolic disorders. The aim of the present study was to identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods: A next-generation sequencing-based miRNA profiling was performed in a case-control study for DN in plasma samples of 23 T2D patients with DN (cases) and 23 T2D without (controls). The main associations were confirmed using quantitative reverse transcription-polymerase chain reaction and tested for replication in an independent case-control collection of 100 T2D patients, 50 with DN and 50 without. Results: From the 381 known mature miRNAs that were found highly expressed in the discovery samples, we observed and replicated an association between increased plasma levels of hsa-miR-152-3p and DN (P = 4.03 × 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were further found to be positively correlated (P = 0.003) to plasma osmolarity, a surrogate marker for solute carrier net activity, whose regulation is controlled by several genes including SLC5A3, one of the predicted targets of hsa-miR-152-3p. Conclusions: We observed strong evidence for the association of hsa-miR-152-3p plasma levels and DN in patients with T2D, confirming an association previously observed in patients with type 1 diabetes.

Mots clés: microRNA-Sequencing; Circulating microRNA; Type 2 diabetes; Diabetic nephropathy; biomarkers; microRNA-Sequencing

Domaines: Endocrinologie et métabolisme; Urologie et Néphrologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Maguelonne Roux, Claire Perret, Eva Feigerlova, Badreddine Mohand Oumoussa, Pierre-Jean Saulnier, et al.. Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in patients with type 2 diabetes. Nephrology Dialysis Transplantation, 2018, 33 (12), pp.2201-2207. ⟨10.1093/ndt/gfx367⟩. ⟨hal-02272317⟩