Is OPRM1 genotype a valuable predictor of VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl?

Abstract

Objective This study was conducted to examine the association between the A118G polymorphism of the OPRM1 gene and the risk of increased VAS scores in patients with colorectal cancer who underwent laparoscopic radical resection for which fentanyl was used. Methods The OPRM1 A118G genotype in subjects were detected. The relationship between the A118G polymorphism of the OPRM1 gene and increased Visual Analogue Scale (VAS) scores throughout the perioperative period was explored. A total of 101 patients receiving fentanyl anesthesia undergoing laparoscopic radical resection of colon tumors at Zhongshan Hospital, Fudan University between July 2018 and December 2020 were investigated in the present study. The relative risk between the A118G polymorphism of the OPRM1 gene and VAS ≥ 4 in the PACU was estimated using the adjusted effect relationship diagram, baseline characteristic analysis, and multiple logistic regression analysis. The relationship between the A118G polymorphism of the OPRM1 gene and VAS in the PACU, as well as perioperative fentanyl usage, was examined after confounders were adjusted. Results Subjects with OPRM1 A118G wild gene A were less sensitive to fentanyl, which was a risk factor for PACU VAS ≥ 4. Before the model was adjusted, the odds ratio (OR) was 14.73 (P = 0.001). After adjusting for age, sex, weight, height, and the duration of surgery, the OR increased to 16.55 (P = 0.001). When adjusting for age, sex, weight, height, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3gene polymorphism, the OR was 19.94 (P = 0.002). Moreover, OPRM1 A118G wild type gene A was found to be a risk factor for increased dosage of fentanyl in the PACU. Before the model was adjusted, the OR reached 16.90 (P = 0.0132). After adjusting for age, sex, body weight, intraoperative fentanyl dosage, surgery duration, and height, the OR was 13.81, (P = 0.0438). When adjusting for age, sex, weight, height, intraoperative fentanyl dosage, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3 gene polymorphism, the OR reached 15.23, (P = 0.0205). Conclusion The A118G polymorphism of the OPRM1 gene carrying wild gene A was a risk factor for VAS ≥ 4 in the PACU. Moreover, it is a risk factor for increased dosage of fentanyl in the PACU.

Pharmacogenetic Approaches in Personalized Medicine for Postoperative Pain Management

“…In the other studies, various DNA extraction methods were utilized: four studies used a conventional phenol-chloroform method [36,46,49,54], four studies employed a Gentra Puregene Blood Kit [34,35,50,51], three studies utilized a QIAamp DNA Blood Mini Kit [43,44,49], two studies used the salting-out method [37,48], two used E.Z.N.A SQ Blood DNA Kit [38,39], while one study each employed a Lab-Aid 820 Midi [31], a MagNA Pure LC DNA Isolation Kit [32], a Wizard Genomic-DNA Purification kit [45], a MagNA Pure LC 2.0 instrument [33], a QIAGEN EZ-1 BioRobot and Blood kit [40], a QIAamp DNA Blood Midi Kit [41], the Guanidinium isothiocyanate method [47], the Chelex method [52], and a PureGene DNA Purification Kit [53].…”

“…OPRM1 encodes the mu opioid receptor, a pivotal drug target. Consequently, the significance of OPRM1 lies in its important involvement in opioid response and pharmacodynamics, as evidenced by several clinical studies [27,[29][30][31][32]40,[49][50][51][52][53], with significant improvement in POP outcomes, allowing for reduced opioid dosage and consequently fewer side effects [27,29,30].…”

“…The impact of COMT haplotypes on pain also appears to vary with gender and ethnic background. Women carrying the COMT HPS haplotype (associated with low COMT activity) tend to experience heightened pain and exhibit decreased hepatic COMT levels [31,70], potentially linked to estrogenic levels.…”