MDR1 Genotypes and Haplotypes Are Closely Associated with Postoperative Fentanyl Consumption in Patients Undergoing Radical Gastrectomy

Fan Zhang,Qin Liao,Jie Hu,Wenxiang Qing,Zhonghua Hu,Jianbin Tong,Tingting Hong

doi:10.1155/2021/5587399

Abstract

Fentanyl is a powerful opioid analgesic, and its analgesic effect is greatly different among individuals. This study was aimed at exploring the effects of multidrug resistance gene-1 (MDR1) genetic variation on postoperative fentanyl consumption. A total of 135 patients, who planned to undergo radical gastrectomy with general anesthesia, were studied. The subjects received patient-controlled analgesia (PCA) by intravenous fentanyl within 48 hours after operation and maintained a numerical rating scale (NRS) score ≤ 3 . The consumption and side effects of fentanyl were recorded within 24 hours and 48 hours after the operation. Single nucleotide polymorphisms (SNPs) of all patients with MDR1 1236C>T, 2677G>T/A, and 3435C>T were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or DNA sequence analysis after PCR. There was no difference in postoperative fentanyl consumption among patients having 2677G>T/A and 3435C>T polymorphisms (all P > 0.05 ). MDR1 1236C>T polymorphisms and haplotypes combined by three SNPs, however, significantly affected postoperative fentanyl consumption (all P < 0.05 ). Moreover, 1236TT genotype carriers consumed more fentanyl during 24 hours ( P = 0.038 ) and 48 hours ( P = 0.003 ) postoperatively. The MDR1 TTT haplotype carriers needed more fentanyl compared with the CGC haplotype carriers during the first 48 hours after surgery ( P = 0.017 ). Nausea, vomiting, and dizziness were not found to have significant differences among the above three SNPs and their haplotypes ( P > 0.05 ). MDR1 1236C>T polymorphism and haplotypes were factors contributing to the individual variability in postoperative fentanyl consumption.

Highlights

Fentanyl is a widely used narcotic analgesic, but its analgesic efficacy has a large interindividual variation among patients [1, 2]
Drug metabolizing enzymes and targets of fentanyl are both likely affected by gene polymorphisms, which in turn affect the analgesic effect of fentanyl [6, 7]
We found that multidrug resistance gene-1 (MDR1) 1236C>T Single nucleotide polymorphisms (SNPs) and the MDR1 gene haplotypes constructed from 1236C>T, 2677G>T/A, and 3435C>T were predictive of individual variations in postoperative fentanyl consumption

Summary

Introduction

Fentanyl is a widely used narcotic analgesic, but its analgesic efficacy has a large interindividual variation among patients [1, 2]. The analgesic effect of fentanyl is affected by many factors, and the gene polymorphism is one of the main factor [3,4,5]. Drug metabolizing enzymes and targets of fentanyl are both likely affected by gene polymorphisms, which in turn affect the analgesic effect of fentanyl [6, 7]. The genes contributing to drug transporters of fentanyl, remain largely unexplored. They may affect the P-gp function by altering protein folding [9]. Haplotypes containing mutant alleles have been shown to exhibit large structural modifications that result in conformational changes in the binding site and subsequent reductions in P-gp activity [12, 13]

Objectives

Methods

Results

Conclusion