Sex Difference in Effect of the OPRM1 Gene A118G (rs1799971) Single‐Nucleotide Polymorphism on the Requirement for Postoperative Fentanyl in Japanese Patients Who Underwent Laparoscopic‐Assisted Colectomy

BACKGROUND: The A118G (rs1799971) single-nucleotide polymorphism (SNP) of the OPRM1 gene, which encodes the μ-opioid receptor, reportedly affects postoperative morphine requirements but not fentanyl requirements. The present study investigated whether this SNP influences postoperative fentanyl requirements after laparoscopic-assisted colectomy (LAC). METHODS: We examined 350 Japanese patients who underwent LAC for colorectal cancer. Postoperative pain was managed with an initial intravenous bolus dose of fentanyl, followed by intravenous fentanyl patient-controlled analgesia (PCA). The primary endpoint was the 12-h postoperative fentanyl requirement, defined as the sum of the initial bolus dose and PCA consumption at 12 h postoperatively, which was normalized to body weight. Genotypes of the A118G SNP were obtained from our previous whole-genome genotyping. Associations between genotypes and pain-related phenotypes were analyzed using the Jonckheere-Terpstra test, followed by the Mann-Whitney U test. Values of p < 0.05 were considered statistically significant. RESULTS: In the total cohort, the 12-h postoperative fentanyl requirement was significantly higher in GG homozygotes than in AA homozygotes (p = 0.022). Among 217 males, it was higher in GG homozygotes than in both AA homozygotes (p = 0.006) and AG heterozygotes (p = 0.038). In contrast, among 133 females, this endpoint was unaffected by the genotype of the A118G SNP. CONCLUSION: In patients who underwent LAC, the OPRM1 A118G SNP significantly influenced postoperative fentanyl requirements in the total cohort, but this effect was observed only in males. These findings indicate a sex-dependent influence of the A118G SNP on postoperative fentanyl requirements in Japanese patients who underwent LAC. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (Trial ID: UMIN000003814).