PMID- 35923832 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220805 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 13 DP - 2022 TI - Transcriptional Down-Regulation of Major Histocompatibility Complex as a Possible Pathogenesis for Meniere's Disease. PG - 938740 LID - 10.3389/fneur.2022.938740 [doi] LID - 938740 AB - OBJECTIVES: This study aimed to determine the underlying pathogenesis of Meniere's disease (MD) using transcriptome analysis. METHODS: Total RNA was extracted from the peripheral blood mononuclear cells of 39 patients with MD and 39 controls. Through microarray analysis for nine patients and controls, the differentially expressed genes (DEGs) of those two groups were screened based on cut-off criteria (|fold changes| > 2.0 and adjusted p-value < 0.05). The functional enrichment analysis of DEGs was performed using Gene Ontology (GO). RESULTS: There were 996 DEGs identified in the MD group: 415 were upregulated and 581 were downregulated. A functional enrichment analysis indicated that the downregulated DEGs were significantly enriched in terms related to immune system processes. Among them, 17 genes were enriched in terms for the major histocompatibility complex (MHC) protein complex, and the relative messenger RNA (mRNA) levels of three markedly downregulated DEGs [fold changes < -5: human leukocyte antigen (HLA)-DMA, HLA-DRB1, and HLA-DPB1] were significantly decreased in another 30 patients with MD compared with normal controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). However, there were no correlations between the expression levels of these three genes and clinical data, such as age, onset age, time course, or hearing threshold. CONCLUSIONS: Our transcriptome analysis showed that the downregulated DEGs in MD were mainly associated with the immune system pathways including the MHC protein complex in MD. Remarkably, a breakdown in immunological tolerance mediated by MHC class II may contribute to the MD development, which has implications for targeted treatment. CI - Copyright (c) 2022 Choi, Oh, Kim, Kim, Park, Choi and Choi. FAU - Choi, Kwang-Dong AU - Choi KD AD - Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, South Korea. FAU - Oh, Eun Hye AU - Oh EH AD - Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea. FAU - Kim, Hyun Sung AU - Kim HS AD - Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea. FAU - Kim, Hyang-Sook AU - Kim HS AD - Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea. FAU - Park, Ji-Yun AU - Park JY AD - Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. FAU - Choi, Seo Young AU - Choi SY AD - Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, South Korea. FAU - Choi, Jae-Hwan AU - Choi JH AD - Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea. LA - eng PT - Journal Article DEP - 20220718 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC9339969 OTO - NOTNLM OT - MHC protein OT - Meniere's disease OT - differentially expressed gene OT - immune system OT - transcriptome analysis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/05 06:00 MHDA- 2022/08/05 06:01 PMCR- 2022/07/18 CRDT- 2022/08/04 02:25 PHST- 2022/05/08 00:00 [received] PHST- 2022/06/20 00:00 [accepted] PHST- 2022/08/04 02:25 [entrez] PHST- 2022/08/05 06:00 [pubmed] PHST- 2022/08/05 06:01 [medline] PHST- 2022/07/18 00:00 [pmc-release] AID - 10.3389/fneur.2022.938740 [doi] PST - epublish SO - Front Neurol. 2022 Jul 18;13:938740. doi: 10.3389/fneur.2022.938740. eCollection 2022.