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Influence of UGT2B7, CYP3A4, and OPRM1 gene polymorphisms on transdermal buprenorphine pain control in patients with critical lower limb ischemia awaiting revascularization

AutorBlanco, Francisco; Muriel, Clemente; Labrador, Jorge; González-Porras, José R.; Lozano, Francisco S.
Palabras clavePeripheral arterial disease
Pain
Polymorphism
Transdermal
CYP3A4
OPRM1
UGT2B7
Buprenorphine
Critical limb ischemia
Genetics
Fecha de publicación2016
EditorJohn Wiley & Sons
CitaciónPain Practice 16(7): 842-849 (2016)
Resumen[Background]: Pain control in critical limb ischemia (CLI) varies considerably between individuals. [Objective]: To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP-TTS) in patients with CLI who are awaiting revascularization. [Methods]: 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. [Results]: 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). [Conclusions]: 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.
URIhttp://hdl.handle.net/10261/168568
Identificadoresdoi: 10.1111/papr.12343
e-issn: 1533-2500
issn: 1530-7085
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