Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

Abstract

BackgroundFentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity.ResultsThis study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test.ConclusionsFentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment.

Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

“…Different dose of morphine. 62 6 ¼ Needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T.…”

Drug metabolism in early infancy: opioids as an illustration

“…Fentanyl is mainly metabolized through N-dealkylation by CYP3A4 to its inactive metabolite, norfentanyl. Two minor routes, responsible for metabolism, are amide hydrolysis to despropionylfentanyl and terminal methyl hydroxylation to hydroxynorfentanyl [34,35]. To gain insight in the CYP3A4 ontogeny and its enzyme activity, Strougo et al investigated the accuracy of maturational scaling approaches as published by Edginton et al, Johnson et al, and Bjorkman et al, respectively [36][37][38].…”

“…Polymorphism of UGT2B7 influences the metabolism of norfentanyl to its glucuronide in adults. However, this is an inactive metabolite and one can question its contribution in case of accumulation (poor metabolizer) [35]. When focusing on disease related non-maturational changes beyond CYP3A4 PG, Vet et al investigated the effects of inflammation in critically ill children on drug metabolism.…”

Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer

“…[21,22] Several SNPs have been confirmed to influence postoperative fentanyl analgesia, such as CYP3A4 ∗1G, CGRP 4218T/C, UGT2B7 , rs7439366, rs4587017, rs1002849, etc. [23–25] In this study, we investigated the genetic effects of P2RX7 rs1718125 polymorphism on analgesic effects of fentanyl in patients with lung cancer after resections.…”