μ-阿片受体基因多态性（A118G）与全膝关节置换术后镇痛吗啡用量变化的相关性

Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty.

作者信息

Chou W-Y, Yang L-C, Lu H-F, Ko J-Y, Wang C-H, Lin S-H, Lee T-H, Concejero A, Hsu C-J

机构信息

Department of Anaesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.

出版信息

Acta Anaesthesiol Scand. 2006 Aug;50(7):787-92. doi: 10.1111/j.1399-6576.2006.01058.x.

DOI:10.1111/j.1399-6576.2006.01058.x

PMID:16879459

Abstract

BACKGROUND

Morphine consumption after a given surgical procedure can vary considerably. Studies show that single nucleotide polymorphism involving the nucleotide position 118 at exon 1 of the mu-opioid receptor gene (OPRM1) may play a role in mediating the effects of opioids. This study was performed to correlate the A118G polymorphism at OPRM1 with morphine consumption in patients undergoing total knee arthroplasty.

METHODS

Post-operative pain was relieved by patient-controlled analgesia (PCA). The analgesic effect was evaluated using a visual analogue scale. Side-effects, such as sedation, nausea and vomiting, and pruritus, were recorded systematically. The genotypes were determined by sequencing polymerase chain reaction-amplified DNA. The differences in demographics and consumed morphine from the PCA device between the different genotypes were tested using one-way analysis of variance. The prevalence of side-effects from morphine and sex distribution were compared using the Kruskal-Wallis test.

RESULTS

One hundred and forty-seven patients were included in the study. Twenty-seven patients who required rescue analgesia were excluded; these patients did not differ demographically or genetically from the 120 who completed the study. Of the latter, 74 were A118 homozygous (AA), 33 were heterozygous (AG) and 13 were G118 homozygous (GG). Group GG consumed significantly more morphine (40.4 +/- 22.0 mg) than group AA (25.3 +/- 15.5 mg) and group AG (25.6 +/- 11.7 mg) during the first 48 h post-operatively. The groups did not differ with respect to reported pain, age, sex, weight and adverse effects.

CONCLUSIONS

G118 homozygotes have a poorer response to morphine for post-operative pain control than A118 homozygotes or heterozygotes. The genotype may thus influence the post-operative response to pain and cause differences in the amounts of analgesic consumed by patients after total knee arthroplasty.

摘要

背景

特定外科手术后吗啡的消耗量可能有很大差异。研究表明，μ-阿片受体基因（OPRM1）外显子1第118位核苷酸的单核苷酸多态性可能在介导阿片类药物的作用中发挥作用。本研究旨在探讨OPRM1基因A118G多态性与全膝关节置换术患者吗啡消耗量之间的相关性。

方法

采用患者自控镇痛（PCA）缓解术后疼痛。使用视觉模拟量表评估镇痛效果。系统记录镇静、恶心、呕吐和瘙痒等副作用。通过对聚合酶链反应扩增的DNA进行测序来确定基因型。使用单因素方差分析测试不同基因型之间的人口统计学差异和PCA设备中吗啡的消耗量。使用Kruskal-Wallis检验比较吗啡副作用的发生率和性别分布。

结果

147例患者纳入本研究。27例需要补救镇痛的患者被排除；这些患者在人口统计学或基因方面与完成研究的120例患者没有差异。在后者中，74例为A118纯合子（AA），33例为杂合子（AG），13例为G118纯合子（GG）。术后48小时内，GG组消耗的吗啡（40.4±22.0mg）明显多于AA组（25.3±15.5mg）和AG组（25.6±11.7mg）。各组在报告的疼痛、年龄、性别、体重和不良反应方面没有差异。