title: Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery.
abstract: Background Fentanyl 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. Results This 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. Conclusions Fentanyl 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.
authors.affiliation: 1 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.|2 Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Shinjyuku-ku, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Muraoka
authors.affiliation: 1 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.affiliation: 3 Department of Oral Health and Clinical Science, Tokyo Dental College, Chiyoda-ku, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: 1 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.affiliation: 1 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: 2 Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Shinjyuku-ku, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wajima
authors.affiliation: 2 Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Shinjyuku-ku, Japan.
authors.forename: Taneaki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: 1 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D057909:Orthognathic Surgery; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D005283:Fentanyl
keywords: Fentanyl; UGT2B7; cold pressor-induced pain test; linkage disequilibrium analysis; perioperative analgesia; single-nucleotide polymorphism