• Postgrad Med J · Dec 2024

    Exploration oxidative stress underlying gastroesophageal reflux disease and therapeutic targets identification: a multi-omics Mendelian randomization study.

    • Jiaxin Shi, Bo Peng, Ran Xu, Xiaoyan Chang, Chenghao Wang, Xiang Zhou, and Linyou Zhang.
    • Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China.
    • Postgrad Med J. 2024 Dec 13.

    IntroductionGastroesophageal reflux disease (GERD) is a chronic inflammatory gastrointestinal disease, which has no thoroughly effective or safe treatment. Elevated oxidative stress is a common consequence of chronic inflammatory conditions.MethodsWe employed Summary-data based MR (SMR) analysis to assess the associations between gene molecular characteristics and GERD. Exposure data were the summary-level data on the levels of DNA methylation, gene expression, and protein expression, which obtained from related methylation, expression, and protein quantitative trait loci investigations (mQTL, eQTL, and pQTL). Outcome data, Genome-wide association study (GWAS) summary statistics of GERD, were extracted from the Ong's study (discovery), the Dönertaş's study (replication), and the FinnGen study (replication). Colocalization analysis was performed to determine if the detected signal pairs shared a causative genetic mutation. Oxidative stress related genes and druggable genes were imported to explore oxidative stress mechanism underlying GERD and therapeutic targets of GERD. The Drugbank database was utilized to conduct druggability evaluation.ResultsAfter multi-omics SMR analysis and colocalization analysis, we identified seven key genes for GERD, which were SUOX and SERPING1, DUSP13, SULT1A1, LMOD1, UBE2L6, and PSCA. SUOX was screened out to be the mediator, which suggest that GERD is related to oxidative stress. SERPING1, SULT1A1, and PSCA were selected to be the druggable genes.ConclusionsThese findings offered strong support for the identification of GERD treatment targets in the future as well as for the study of the oxidative stress mechanism underlying GERD.© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…