Influence of UGT 2B7 , OPRM 1 and ABCB 1 G ene Polymorphisms on Postoperative Morphine Consumption

Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT 2 B 7 , OPRM 1 and ABCB 1 polymorphisms for interindividual variability in morphine‐induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24 hr after initiation of analgesia through a patient‐controlled analgesia ( PCA ) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies found positive for morphine in routine forensic analysis. Patients homozygous for UGT 2 B 7 802 C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB 1 1236 T and 3435 T , as well as to OPRM 1 118 A . The dose of morphine in patients included in this study was significantly related to variation in UGT 2 B 7 T 802 C . Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNP s in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.