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

Gene. 2019 Jun 20:702:114-122. doi: 10.1016/j.gene.2019.02.105. Epub 2019 Mar 19.

Abstract

Aim: 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.

Method: 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.

Results: 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.

Conclusion: LRP1 and CHOP might be involved in DPN pathogenesis and progression, thus providing opportunities for early detection and treatment.

Keywords: C/EBP homologous protein; Diabetic peripheral neuropathy; Low-density lipoprotein receptor-related protein-1; Pathogenesis; T2DM.

MeSH terms

  • Adult
  • Blood Cells / metabolism
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Neuropathies / blood*
  • Diabetic Neuropathies / diagnosis
  • Diabetic Neuropathies / genetics
  • Diabetic Neuropathies / physiopathology
  • Female
  • Gene Expression
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / blood*
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Male
  • Middle Aged
  • Neural Conduction
  • RNA, Messenger / metabolism
  • Transcription Factor CHOP / blood*
  • Transcription Factor CHOP / genetics

Substances

  • DDIT3 protein, human
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • RNA, Messenger
  • Transcription Factor CHOP