title: Influence of UGT2B7, CYP3A4, and OPRM1 Gene Polymorphisms on Transdermal Buprenorphine Pain Control in Patients with Critical Lower Limb Ischemia Awaiting Revascularization.
abstract: Pain control in critical limb ischemia (CLI) varies considerably between individuals.
  
  
  
  To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP-TTS) in patients with CLI who are awaiting revascularization.
  
  
  
  One hundred and seven patients with CLI were treated with BUP-TTS. The following were analyzed: (1) pain perception (visual analog scale (VAS) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (UGT2B7), cytochrome (CYP3A4), and μ-opioid receptor (OPRM1) gene polymorphisms.
  
  
  
  Ninety-three patients completed the study. The VAS score by the fourth day of analgesia dropped from 6.82 to 3.38 (P < 0.05). The analgesic response to BUP-TTS was greater in men than in women (P = 0.019). Patients who were AA homozygotes for the CYP3A4 gene showed the best response to analgesic treatment (P = 0.003). The combination of the CYP3A4 gene with UGT2B7 or OPRM1 was favorable to the effect of the CYP3A4 gene (P = 0.045 and P = 0.026, respectively). The combination of UGT2B7 with OPRM1 was ineffective (P = 0.648). The 3 polymorphisms together had no effect on response to treatment (P = 0.461).
  
  
  
  BUP-TTS is efficacious in the control of pain in patients with CLI. The homozygous AA carriers of the CYP3A4 gene respond better to treatment with BUP-TTS.
authors.affiliation: General Surgery Department, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco
authors.affiliation: Anesthesiology and Reanimation Department, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Clemente
authors.initials: C
authors.lastname: Muriel
authors.affiliation: Hematology Department, Hospital Universitario de Burgos, Burgos, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Labrador
authors.affiliation: Hematology Department, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Gonzalez-Porras
authors.affiliation: Molecular Medicine Unit-Medicine Department, Facultad de Medicina-IBSAL-Universidad de Salamanca-CSIC, Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Gonzalez-Sarmiento
authors.affiliation: Angiology and Vascular Surgery Department, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Lozano
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002047:Buprenorphine / Q000008:administration & dosage*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007511:Ischemia / Q000150:complications; D035002:Lower Extremity / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase
keywords: CYP3A4; OPRM1; UGT2B7; buprenorphine; critical limb ischemia; genetics; pain; peripheral arterial disease; polymorphism; transdermal