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MDR/CYP3A4/OPRM 基因多态性与中国女性剖宫产术后芬太尼镇痛效果的相关性。

Association between MDR/CYP3A4/OPRM gene polymorphisms and the post-caesarean fentanyl analgesic effect on Chinese women.

机构信息

Department of Pain Clinic, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China.

Department of Anesthesiology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.

出版信息

Gene. 2018 Jun 30;661:78-84. doi: 10.1016/j.gene.2018.03.081. Epub 2018 Mar 27.

DOI:10.1016/j.gene.2018.03.081
PMID:29601950
Abstract

OBJECTIVE

Our study aimed to evaluate the association between the multidrug resistance 1 (MDR)/cytochrome P450 3A4 (CYP3A4)/μ-opioid receptor (OPRM) gene polymorphisms and the post-caesarean analgesic effect of fentanyl on Chinese women.

METHODS

We recruited 240 patients who received lower segment caesarean section surgeries. Sanger sequencing was used to analyze the MDR1236C > T/CYP3A4*1G/OPRMA118G polymorphisms. We evaluated post-operative fentanyl consumption and the effect of intravenous analgesia in patients with different genotypes.

RESULTS

  1. Subjects with the TT genotype at the 1236C > T polymorphism in the MDR gene consumed significantly more fentanyl than that consumed by subjects with the CC and CT genotypes in the first post-operative 24 h and 48 h (P < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually increased immediately after surgery and in the first post-operative 24 h. 2. Subjects with the CYP3A4*1G/1G genotype needed less fentanyl to achieve pain control than that needed by subjects carrying the CYP3A41/1 and CYP3A41/*1G genotypes in the first post-operative 24 h and 48 h (P < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually decreased immediately after surgery and in the first post-operative 24 h. 3. Subjects with the GG genotype at the A118G polymorphism in the OPRM gene consumed significantly more fentanyl than that consumed by subjects with the AA and AG genotypes in the first post-operative 24 h and 48 h (P < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually increased immediately after surgery and in the first post-operative 24 h. 4. There were no significant differences in the adverse reactions to fentanyl in patients with different genotypes (P > 0.05).

CONCLUSION

These results indicated that the MDR/CYP3A4/OPRM gene polymorphisms influenced the fentanyl consumption and the physiological effects of intravenous analgesia in the Chinese women who received lower segment caesarean section surgeries. Moreover, the present study provides an important foundation and theoretical evidence for the gene-directed rationalization and individualization of medication before caesarean section surgeries.

摘要

目的

本研究旨在评估多药耐药 1 型(MDR)/细胞色素 P450 3A4(CYP3A4)/μ-阿片受体(OPRM)基因多态性与芬太尼在中国女性剖宫产术后镇痛效果之间的关系。

方法

我们招募了 240 名接受下段剖宫产术的患者。采用 Sanger 测序分析 MDR1236C>T/CYP3A4*1G/OPRMA118G 多态性。我们评估了不同基因型患者术后芬太尼的消耗和静脉镇痛效果。

结果

  1. MDR 基因 1236C>T 多态性 TT 基因型患者在术后 24 小时和 48 小时内消耗的芬太尼明显多于 CC 和 CT 基因型患者(P<0.05),MAP/HR/Cor/Ang-1 水平在术后立即和术后 24 小时内逐渐升高。2. CYP3A4*1G/1G 基因型患者在术后 24 小时和 48 小时内需要的芬太尼量明显少于 CYP3A41/1 和 CYP3A41/*1G 基因型患者(P<0.05),MAP/HR/Cor/Ang-1 水平在术后立即和术后 24 小时内逐渐下降。3. OPRM 基因 A118G 多态性 GG 基因型患者在术后 24 小时和 48 小时内消耗的芬太尼明显多于 AA 和 AG 基因型患者(P<0.05),MAP/HR/Cor/Ang-1 水平在术后立即和术后 24 小时内逐渐升高。4. 不同基因型患者对芬太尼的不良反应无显著差异(P>0.05)。

结论

这些结果表明,MDR/CYP3A4/OPRM 基因多态性影响中国女性下段剖宫产术后芬太尼的消耗和静脉镇痛的生理效应。此外,本研究为剖宫产术前药物的基因导向合理化和个体化提供了重要基础和理论依据。

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