Expression of LRP1 and CHOP genes associated with peripheral neuropathy in type 2 diabetes mellitus: Correlations with nerve conduction studies

• Published in: Gene Vol. 702; pp. 114 - 122
• Main Authors: El-Horany, Hemat El-Sayed, Watany, Mona Mohamed, Hagag, Rasha Youssef, El-Attar, Shimaa Hassan, Basiouny, Mohamed Abdelaziz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.06.2019
• Subjects: apoptosis; blood cells; C/EBP homologous protein; diabetes mellitus; Diabetic peripheral neuropathy; electrophysiology; endoplasmic reticulum; gene expression; genes; hyperlipidemia; low density lipoprotein; Low-density lipoprotein receptor-related protein-1; messenger RNA; nerve tissue; Pathogenesis; peripheral nervous system diseases; protein metabolism; quantitative polymerase chain reaction; T2DM; T2DM; Diabetic peripheral neuropathy; Pathogenesis; C/EBP homologous protein; Low-density lipoprotein receptor-related protein-1
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2019.02.105

Diabetic peripheral neuropathy (DPN) is a frequent and debilitating complication of diabetes mellitus. The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional cell surface receptor playing critical roles in lipoprotein metabolism and several cell signaling processes. C/EBP homologous protein (CHOP) is a main conduit to endoplasmic reticulum stress-induced apoptosis. We aimed to investigate LRP1 and CHOP gene expression in peripheral blood cells of type 2 diabetes mellitus (T2DM) subjects to clarify its possible relation to DPN pathogenesis. The study included 20 non-complicated T2DM subjects, 20 subjects with DPN and 20 healthy controls. Quantitative real time PCR was used to study gene expression. There was a significant reduction in LRP1 mRNA expression and a significant increase in CHOP mRNA expression in subjects with DPN compared to non-complicated group and healthy controls. Both LRP1 and CHOP expression levels were inversely correlated, and both showed significant correlation with HbA1c, hyperlipidemia, hs-CRP, and different electrophysiological parameters. Receiver operating characteristics (ROC) analysis suggested that both LRP1 and CHOP mRNA expression and hs-CRP levels had great potential advantages to predict the progression of DPN. LRP1 and CHOP might be involved in DPN pathogenesis and progression, thus providing opportunities for early detection and treatment. •DPN patients peripheral blood cells show significantly higher LRP-1 and lower CHOP expression as compared to healthy and non-complicated diabetic patients.•Both LRP1 and CHOP expression levels were inversely correlated, and both are significantly correlated with hyperlipidemia, HbA1c, hs-CRP.•The present study advances the field by identifying LRP1 as a player in DPN pathogenesis and progression.