NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action

Background and objectiveNSAIDs 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.MethodsWhole 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.ResultsGene 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.ConclusionOur 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.

Automated summary

This study suggests a potential role of epigenetics in the mechanisms of action of NSAIDs. The analysis of DNA methylation profiles revealed several biological pathways related to NSAIDs' function. However, due to the lack of statistically significant findings, these results should be interpreted with caution as exploratory and hypothesis-generating.