RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Clin Exp Immunol. 2018 Apr;192(1):33-45. doi: 10.1111/cei.13083. Epub 2017 Dec 11.

Abstract

To date, the pathogenesis of Ménière's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system-related genes and sporadic MD. The whole RNA-sequencing (RNA-seq) technology was used to analyse the transcriptome of peripheral blood mononuclear cells of three MD patients and three control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log2 fold change| > 1 and P < 0·05). Gene ontology (GO) enrichment analysis illustrated that immune relevant factors played a key role in the pathogenesis of MD. Of 366 DEGs, we focused upon analysing the possible immune-related genes, among which the significantly up-regulated genes [glutathione S-transferase mu 1 (GSTM1), transmembrane protein 176 (TMEM176)B, TMEM176A] and down-regulated genes [solute carrier family 4 member (SLC4A)10 and SLC4A1] especially drew our attention. The mRNA expression levels of GSTM1, TMEM176B, TMEM176A, SLC4A1 and SLC4A10 were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The serum concentration of GSTM1, TMEM176B and SLC4A10 proteins were measured by enzyme-linked immunosorbent assay (ELISA). Considering the results of qRT-PCR and ELISA, it was noteworthy that GSTM1 exhibited the highest fold change between two groups, which was consistent with the deep sequencing results by RNA-seq. In conclusion, our study first offers a new perspective in MD development on the basis of RNA expression patterns, suggesting that immune factors might be involved in the MD pathogenesis. Remarkably, GSTM1 might be a possible candidate gene for the diagnostic biomarker of MD and provides the basis for further biological and functional investigations.

Keywords: Ménière's disease; RNA sequencing; immune system; transcriptome.

MeSH terms

  • Biomarkers / blood
  • Case-Control Studies
  • Gene Expression Profiling*
  • Glutathione Transferase / blood
  • Glutathione Transferase / genetics
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Membrane Proteins / blood
  • Membrane Proteins / genetics
  • Meniere Disease / immunology*
  • Meniere Disease / pathology*
  • Sequence Analysis, RNA
  • Sodium-Bicarbonate Symporters / blood
  • Sodium-Bicarbonate Symporters / genetics
  • Transcriptome

Substances

  • Biomarkers
  • Membrane Proteins
  • SLC4A10 protein, human
  • Sodium-Bicarbonate Symporters
  • TMEM176B protein, human
  • Glutathione Transferase
  • glutathione S-transferase M1