Gene regulation associated with the onset of postoperative delirium

Abstract

Postoperative delirium is a common surgical complication. The underlying pathophysiology has not yet been elucidated. Prior work in this laboratory has identified differentially methylated positions associated with specific genes in the context of both surgery and postoperative delirium. Polymerise chain reaction primers were developed for five genes: Monoamine oxidase A (MAOA), catechol-O-methyltransferase (COMT), nuclear receptor subfamily 4 group A member 3 (NR4A3), RNA binding motif protein 8A RBM8A, and NIPA like domain containing 3 (NIPAL3). Blood samples were collected from patients across three timepoints, preoperatively, one day postoperatively and four or seven days postoperatively. 20% of patients who underwent surgery developed postoperative delirium as assessed by a trained practitioner. Relative gene expression in blood samples was calculated at all three time points for each gene using quantitative real-time polymerise chain reaction. Relative gene expression was altered in the postoperative interim for all genes analysed. Differences in relative gene expression in those who developed delirium versus those who did not develop delirium were not statistically significant. Levels of methylation at sites associated with these genes did not correlate with relative gene expression. Preoperative data demonstrated a link between blood pressure and rates of delirium. Follow-up data demonstrated an inverse correlation between delirium and readmission rates. This study revealed that gene expression is altered in the postoperative period. Further studies into the relationship between delirium and alterations in gene expression are necessary to draw further conclusions.