An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia

Abstract

This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA expression was significantly reduced at all time points, with lowest level of −68%. DNMT3a and DNMT3b decreased by 65 and 71%, respectively. Inflammatory cytokines IL6 and TNFα mRNA levels showed a trend for increased expression at early time-points to end with a significant decrease at 48 h after surgery. This exploratory study revealed for the first time intraoperative global DNA hypomethylation in patients undergoing major breast surgery under general anesthesia with fentanyl. The alterations of global DNA methylation here observed seem to be in agreement with DNMTs gene expression changes. Furthermore, based on perioperative variations of IL6 and TNFα gene expression, we hypothesize that DNA hypomethylation may occur as a response to surgical stress rather than to opiate exposure.

Outcomes of early social experiences on glucocorticoid and endocannabinoid systems in the prefrontal cortex of male and female adolescent rats

“…Total RNA was extracted according to the method of Chomczynski and Sacchi (2006). Each sample was subjected to DNAse treatment and converted to cDNA with the GeneAmp RNA PCR kit (Life Technologies Italia, Italy) as previously described (Caputi et al, 2019(Caputi et al, , 2021. The qRT-PCR analysis was performed on a StepOne Real-Time PCR System (Life Technologies, Italy) using the SYBR Green PCR MasterMix (Life Technologies, Italy).…”

A decrease in NR2B expression mediated by DNA hypermethylation induces perioperative neurocognitive disorder in aged mice

“…However, similar results were observed in the processes of aging and carcinogenesis. 9 , 38 Indeed, studies on PND have also observed global DNA hypomethylation, 11 , 39 and DNA hypermethylation of several genes (e.g. glucocorticoid receptor, Arc, Bdnf, Reln, PSD‐95 ), 10 , 40 , 41 indicating that the global DNA methylation status did not necessarily reflect the methylation of specific genes.…”

Global DNA hypomethylation in hysterectomy: An 8-year follow-up study from Haryana, India

“…Only a few studies thus far have evaluated post-operative acute epigenetic changes for any kind of surgery (except bariatric surgery). [13][14][15] Studies have shown alterations in gene-speci c and global DNA methylation levels during and after the surgery; however, no consistent trend has been reported. [13][14][15] Again, no study has explored long-term and persistent epigenetic changes after the surgery (except in the case of bariatric surgery).…”