Combined Catechol-O-Methyltransferase and μ-Opioid Receptor Gene Polymorphisms Affect Morphine Postoperative Analgesia and Central Side Effects

BACKGROUND: Previous studies have generated controversial results regarding the influence of the genetic variations of μ-opioid receptors on morphine analgesia and opioid-related side effects in the postoperative period. Few studies have been conducted attempting to assess the combined effects of variation within ≥2 genes in relation to morphine response. In this study, we investigated whether combined catechol-O-methyltransferase and μ-opioid receptor polymorphisms contribute to the morphine response in postoperative analgesia. METHODS: One hundred two surgical patients were enrolled in this prospective, observational study. All patients received general anesthesia and were screened for μ-opioid receptor polymorphism A118G (Asn40Asp) and catechol-O-methyltransferase G1947A (Val158Met) polymorphism using a blood sample of DNA. Patient-controlled analgesia was provided postoperatively and morphine consumption was observed. Any pain at rest or side effects were measured with rating scales. RESULTS: The heterozygous patients with μ-opioid receptor A118G and catechol-O-methyltransferase G1947A mutation consumed significantly less morphine in the postanesthetic recovery room and 48 hours after surgery compared with homozygous patients of the A118 variant. Nausea and sedation scores were also significantly lower during all observed postoperative periods for heterozygous patients and only 2 patients (18%) from this group received antinausea treatment. CONCLUSION: This study has demonstrated the importance of the gene-gene approach in understanding the morphine response in patients after lower abdominal surgery. More studies are needed to characterize the combined effects of multiple genes and demographic as well as clinical variables in predicting the correct morphine dosage and corresponding opioid-related side effects.