Objective To explore the correlation between the individual difference in postoperative dosage of fentanyl and polymorphisms of several genes related to metabolic enzymes (CYP3A4*1G, CYP3A5*3, COMT Val158Met) and opioid receptor (OPRM1 rs563649).

Methods A total of 91 patients receiving fentanyl anesthesia undergoing laparoscopic radical resection of colon tumors at Zhongshan Hospital, Fudan University from October 2018 to March 2020 were investigated in the present study. Peripheral venous blood samples were collected before surgery, and the Sanger method was used for gene sequencing of CYP3A4*1G, CYP3A5*3, OPRM1 rs563649 and COMT Val158Met. The postoperative analgesic requirement of fentanyl and VAS score were recorded after the operation. The gene polymorphisms were analyzed to investigate whether these factors contributed to postoperative opioid doses.

Results The mutation frequencies of CYP3A4*1G, CYP3A5*3, OPRM1 rs563649 and COMT Val158Met alleles in colon cancer patients were 31.87%, 65.93%, 9.40%, and 26.92%, respectively. Patients with CYP3A4*1G/*1G mutation homozygous genotypes needed less fentanyl to achieve pain control on the first and second postoperative days (P < 0.05). There were no significant differences in fentanyl consumption between the different genotypes of CYP3A5*3, OPRM1 rs563649, and COMT Val158Met alleles. There was no significant difference in the incidences of adverse reactions such as nausea, vomiting, and sedation among CYP3A4*1G, CYP3A5*3, OPRM1 rs563649, and COMT Val158Met genotypes.

Conclusions In the absence of significant differences in postoperative pain scores, postoperative fentanyl requirements are reduced in patients with CYP3A4*1G/*1G mutant homozygotes. This finding may provide valuable information for personalized pain treatment.