OPRM1 基因 A118G 多态性导致全膝关节置换术后女性患者吗啡消耗的差异。

A118G polymorphism of OPRM1 gene caused different morphine consumption in female patients after total knee replacement.

机构信息

Department of Anesthesiology, National Cheng Kung University Hospital, Tainan, Taiwan; Institute of Clinical Pharmacy and Pharmaceutical Science, National Cheng Kung University, Taiwan.

Department of Orthopaedics, Kaohsiung Veterans General Hospital, Taiwan; Nursing College, Fooyin University, Kaohsiung, Taiwan.

出版信息

J Orthop Sci. 2021 Jul;26(4):629-635. doi: 10.1016/j.jos.2020.05.017. Epub 2020 Aug 13.

DOI:10.1016/j.jos.2020.05.017

PMID:32800527

Abstract

BACKGROUND

We intended to clarify the effect of gender and A118G polymorphism of Opioid Receptor μ1 (OPRM1) on the required morphine for patients to maintain Visual Analogue Scale ≦ 3 for post-operative pain control after total knee replacement (TKR).

METHODS

With approval from Institutional Review Board (IRB) and obtainment of informed consents, 111 patients undergoing primary TKR were enrolled without violating the exclusion criteria, including previous history of allergy to morphine, alcohol or substance abuse, use of psychotropic medications, morbid obesity of body mass index (BMI) > 40 kg/m, chronic pain with evidence of central sensitization, and uncooperative use of patient controlled analgesia (PCA) device. The amount of PCA-delivered morphine for pain control and the 'demand' (the count of button pushing for requiring pain medication from PCA) were recorded at 3, 6, 12, 24, 36, 48 and 72 h after the operation. One-way ANOVA with post-hoc test by Scheffe's method was adopted for statistical analysis of each variant (AA, AG, GG). The side-effects (nausea, vomiting and sedation) from morphine were recorded. P < 0.05 was considered to be statistically significant.

RESULTS

With sequencing by ABI PRISM 310 Genetic Analyser, we disclosed that the allele frequency was 75.5% for the A allele (female: 77.5%, male: 69.6%) and 24.5% for the G allele (female: 22.5%, male: 30.4%). The frequency of genotype occurrence was 61.3% for AA, 24.3% for AG and 14.4% for GG. Female patients of homozygous G118G of OPRMI required more morphine from PCA device for post-operative pain control than patients of AA and AG genotypes. No significant difference in morphine consumption for post-operative pain control was disclosed among three genotypes for male patients.

CONCLUSIONS

The impact caused by G118G polymorphism of OPRM1 on requirement of morphine consumption for post-operative pain control is potentially gender-linked.

摘要

背景

我们旨在阐明性别和阿片受体μ1（OPRM1）A118G 多态性对全膝关节置换（TKR）后维持视觉模拟评分≦3 的术后疼痛控制所需吗啡的影响。

方法

在获得机构审查委员会（IRB）的批准并获得知情同意后，我们纳入了 111 名接受初次 TKR 的患者，这些患者没有违反排除标准，包括对吗啡、酒精或药物滥用过敏史、使用精神药物、体重指数（BMI）>40kg/m2 的病态肥胖、有中枢敏化证据的慢性疼痛以及不合作用于患者自控镇痛（PCA）设备。记录术后 3、6、12、24、36、48 和 72 小时时 PCA 输送的吗啡量和“需求”（PCA 要求使用止痛药的按钮按压次数）。采用单因素方差分析（one-way ANOVA）和 Scheffe 事后检验法对每个变体（AA、AG、GG）进行统计学分析。记录吗啡的副作用（恶心、呕吐和镇静）。P<0.05 被认为具有统计学意义。

结果

通过 ABI PRISM 310 遗传分析仪测序，我们揭示等位基因频率为 A 等位基因 75.5%（女性：77.5%，男性：69.6%）和 G 等位基因 24.5%（女性：22.5%，男性：30.4%）。基因型发生的频率为 AA 61.3%、AG 24.3%和 GG 14.4%。OPRMI 纯合 G118G 的女性患者比 AA 和 AG 基因型的患者需要更多的 PCA 设备吗啡来控制术后疼痛。未发现男性患者三种基因型之间用于术后疼痛控制的吗啡消耗存在显著差异。