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

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) $\text{score}\le 3$ . 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.