Effect of A118G (rs1799971) single-nucleotide polymorphism of the μ-opioid receptor OPRM1 gene on intraoperative remifentanil requirements in Japanese women undergoing laparoscopic gynecological surgery

Abstract

Aim: Abundant data are available on the effect of the A118G (rs1799971) single-nucleotide polymorphism (SNP) of the μ-opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements.

Methods: We investigated 333 Japanese women, aged 21-69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann-Whitney U test.

Results: The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039).

Conclusions: The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.

Keywords: bispectral index; laparoscopic gynecologic surgery; mu‐opioid receptor gene; remifentanil; single‐nucleotide polymorphism.

FIGURE 1

Association between genotypes of the A118G single‐nucleotide polymorphism (SNP) and (A) average propofol infusion rate, (B) average remifentanil infusion rate, (C) the average intraoperative bispectral index (BIS), and (D) total postoperative fentanyl dose. The data are expressed as box and whisker plots. The solid line in the box depicts the median. Ends of the box represent the 25th and 75th percentiles. Whiskers represent the 10th and 90th percentiles. Values of p, based on the Mann–Whitney U test, are depicted.