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尿苷二磷酸葡萄糖醛酸基转移酶2B7(UGT2B7)变体对术后丁丙诺啡镇痛的影响。

Influence of uridine diphosphate-glucuronyltransferase 2B7 (UGT2B7) variants on postoperative buprenorphine analgesia.

作者信息

Sastre José A, Varela Gonzalo, López Mónica, Muriel Clemente, González-Sarmiento Rogelio

机构信息

Department of Anesthesiology and Pain Clinic, Cardiothoracic division, University Hospital and IBSAL, Salamanca, Spain.

出版信息

Pain Pract. 2015 Jan;15(1):22-30. doi: 10.1111/papr.12152. Epub 2013 Nov 20.

Abstract

BACKGROUND

Genetic factors are known to influence individual differences in pain and sensitivity to analgesics. Different genetic polymorphisms in opioid-metabolizing enzymes that can affect the analgesic response to opioids have been proposed. This study investigates a possible difference in the response to postoperative buprenorphine analgesia related to the presence of different isoforms (cytosine or thymine substitution at nucleotide 802) of UGT2B7 gene.

METHODS

Transdermal buprenorphine was administered to 91 patients who underwent muscle-sparing thoracotomy. UGT2B7 polymorphism at locus C802T (His268Tyr) was detected using a PCR Taqman-based procedure. The severity of postoperative pain at rest and during coughing or deep inspiration was assessed by visual analog scale score after surgery. Hospital stay and perioperative opioid consumption were collected.

RESULTS

Genotype frequencies were 18.4% for UGT2B7*1/1, 52.9% for UGT2B71/2, and 28.7% for UGT2B72/2. VAS pain scores at rest were statistically similar among the groups except at 24, 60, and 120 hours (UGT2B72/2 genotype showing higher pain scores). Patients with the UGT2B72/2 genotype showed higher VAS scores triggered by coughing after the 48 hours (P < 0.05). In addition, patients with this genotype reported a higher prevalence of severe pain after 48 postoperative hours (P < 0.05). Thirty-eight percent of patients carrying genotype UGT2B72/2 experienced severe pain in a final survey vs. 17% in the group with UGT2B71/*1 (P = 0.36).

CONCLUSIONS

The presence of the SNP 802C>T UGT2B7 (UGT2B7*2/*2) is associated with a worse analgesic response to transdermal buprenorphine in the postoperative period of thoracic surgery.

摘要

背景

已知遗传因素会影响个体对疼痛的差异以及对镇痛药的敏感性。有人提出,参与阿片类药物代谢的酶存在不同的基因多态性,可能会影响对阿片类药物的镇痛反应。本研究调查了与UGT2B7基因不同亚型(核苷酸802处胞嘧啶或胸腺嘧啶替代)的存在相关的术后丁丙诺啡镇痛反应的可能差异。

方法

对91例行保留肌肉胸廓切开术的患者给予经皮丁丙诺啡。采用基于PCR Taqman的方法检测C802T位点(His268Tyr)的UGT2B7多态性。术后通过视觉模拟量表评分评估静息时以及咳嗽或深吸气时的术后疼痛严重程度。收集住院时间和围手术期阿片类药物消耗量。

结果

UGT2B7*1/1基因型频率为18.4%,UGT2B71/2基因型频率为52.9%,UGT2B72/2基因型频率为28.7%。除24、60和120小时外,各组静息时的视觉模拟量表疼痛评分在统计学上相似(UGT2B72/2基因型的疼痛评分更高)。UGT2B72/2基因型的患者在48小时后咳嗽引发的视觉模拟量表评分更高(P<0.05)。此外,该基因型的患者术后48小时后重度疼痛的发生率更高(P<0.05)。在最终调查中,携带UGT2B72/2基因型的患者中有38%经历了重度疼痛,而UGT2B71/*1组为17%(P = 0.36)。

结论

UGT2B7基因802C>T单核苷酸多态性(UGT2B7*2/*2)的存在与胸外科手术后经皮丁丙诺啡的镇痛反应较差有关。

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