Journal article
NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action
Clinical and experimental medicine, Vol.23(7), pp.3509-3516
11/2023
DOI: 10.1007/s10238-023-01119-9
PMID: 37341931
Abstract
BACKGROUND AND OBJECTIVE NSAIDs inhibit cyclooxygenase, but their role in aging and other diseases is not well understood. Our group previously showed the potential benefit of NSAIDs in decreasing the risk of delirium and mortality. Concurrently, epigenetics signals have also been associated with delirium. Therefore, we sought to find differentially methylated genes and biological pathways related to exposure with NSAIDs by comparing the genome-wide DNA methylation profiles of patients with and without a history of NSAIDs use. METHODS Whole blood samples were collected from 171 patients at the University of Iowa Hospital and Clinics from November 2017 to March 2020. History of NSAIDs use was assessed through a word-search function in the subjects' electronic medical records. DNA was extracted from the blood samples, processed with bisulfite conversion, and analyzed using Illumina's EPIC array. The analysis of top differentially methylated CpG sites and subsequent enrichment analysis were conducted using an established pipeline using R statistical software. RESULTS Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed several biological pathways relevant to NSAIDs' function. The identified GO terms included "arachidonic acid metabolic process," while KEGG results included "linoleic acid metabolism," "cellular senescence," and "circadian rhythm." Nonetheless, none of the top GO and KEGG pathways and the top differentially methylated CpG sites reached statistical significance. CONCLUSION Our results suggest a potential role of epigenetics in the mechanisms of the action of NSAIDs. However, the results should be viewed with caution as exploratory and hypothesis-generating given the lack of statistically significant findings.
Details
- Title: Subtitle
- NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action
- Creators
- Pedro S Marra - Stanford UniversityYoshitaka Nishizawa - Osaka University of Pharmaceutical SciencesTakehiko Yamanashi - Stanford UniversityEleanor J Sullivan - University of IowaKatie R Comp - University of IowaKaitlyn J Crutchley - University of Nebraska Medical CenterNadia E Wahba - Oregon Health & Science UniversityKazuki Shibata - Sumitomo Dainippon PharmaTsuyoshi Nishiguchi - Stanford UniversityKyosuke Yamanishi - Stanford UniversityNicolas O Noiseux - University of IowaMatthew D Karam - University of IowaGen Shinozaki - Stanford University
- Resource Type
- Journal article
- Publication Details
- Clinical and experimental medicine, Vol.23(7), pp.3509-3516
- DOI
- 10.1007/s10238-023-01119-9
- PMID
- 37341931
- eISSN
- 1591-9528
- Language
- English
- Electronic publication date
- 06/21/2023
- Date published
- 11/2023
- Academic Unit
- Psychiatry; Orthopedics and Rehabilitation; Neurosurgery
- Record Identifier
- 9984436286802771
Metrics
4 Record Views