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).