阿片类药物便秘不良反应与基因多态性关联性研究

杨静; 张新宇; 郑磊; 管玉瑶; 常温来; 林忠琨; 张雅慧; 付正

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阿片类药物便秘不良反应与基因多态性关联性研究

更新时间：2025-09-25

- 阿片类药物便秘不良反应与基因多态性关联性研究
- Study on the Relationship between Adverse Reaction of Opioid Constipation and Gene Polymorphism
- 中国药房 2025年页码：1-6
- 作者机构：
  
  1.山东医学高等专科学校，济南 250031
  2.山东省立第三医院药学部，济南 250031
  3.中国海洋大学，山东青岛 266000
  4.山东省立医院药学部，济南 250031
- 作者简介：
  
  副主任药师，博士。研究方向：临床药学。E-mail：15853199531@163.com
  教授。研究方向：药学。E-mail：fz19820528@163.com
- 基金信息：
  
  山东省药品不良反应监测中心委托研究课题(2021sdadrky03);山东省医学会临床科研专项资金课题(YXH2020ZX047);山东省医药卫生科技发展计划项目(2017WS101);济南市科技局临床医学科技创新计划(202134016)
- DOI：
  中图分类号： R971
- 网络出版日期：2023-08-11，
- 稿件说明：
移动端阅览
杨静,张新宇,郑磊,等.阿片类药物便秘不良反应与基因多态性关联性研究[J].中国药房,

YANG Jing,ZHANG Xinyu,ZHENG Lei,et al.Study on the Relationship between Adverse Reaction of Opioid Constipation and Gene Polymorphism[J].ZHONGGUO YAOFANG,
杨静,张新宇,郑磊,等.阿片类药物便秘不良反应与基因多态性关联性研究[J].中国药房, DOI：10.6039/j.issn.1001-0408...01.

YANG Jing,ZHANG Xinyu,ZHENG Lei,et al.Study on the Relationship between Adverse Reaction of Opioid Constipation and Gene Polymorphism[J].ZHONGGUO YAOFANG, DOI：10.6039/j.issn.1001-0408...01.

摘要

目的

探讨基因多态性对阿片类药物引起便秘不良反应的影响。

方法

首先对阿片类药物不良反应相关基因组学研究进行循证医学资料分析，选取目标基因；随后纳入50例使用阿片类药物后出现严重便秘和50例未出现药物不良反应的癌痛患者作为试验组和对照组，进行1：1配对研究；利用聚合酶链式反应（PCR）和原位杂交法对目标基因进行检测并进行关联性分析。最后结合患者年龄、性别、用药剂量、用药时长等临床资料，采用多因素Logistic回归分析，探讨阿片类药物便秘不良反应发生的相关预测因素。

结果

共选取

CYP2D6

、

CYP3A5*3

、

ABCB1

、

OPRM1

作为目标基因进行检测；SNPStats 遗传模型分析显示

CYP3A5*3

（058rs776746，A

G）、

OPRM1

（047rs1799971，A

G）多态性与阿片类药物引起便秘不良反应具有相关性；其中

CYP3A5*3

（058rs776746）GG、AG型，

OPRM1

（047rs1799971）AA、AG型是阿片类药物引起严重便秘的危险因素。同时结合临床资料进行Logistic 回归分析显示：用药时长、

CYP3A5*3、OPRM1

基因多态性均可作为患者使用阿片类药物发生便秘的预测因素。

结论

CYP3A5*3

（058rs776746，A

G）、

OPRM1

（047rs1799971，A

G）多态性与阿片类药物引起便秘具有相关性，有望成为阿片类药物不良反应临床预测指标；在用药时间较长的患者中更应关注严重便秘的发生。

Abstract

Objective

To investigate the effect of gene polymorphism on adverse reactions（ADR） of constipation induced by opioids.Methods We first conducted evidence-based medical data analysis on the research of genes related to opioid adverse reactions

and selected target genes; Then 50 patients with severe constipation and 50 patients with cancer pain without adverse drug reactions after taking opioid drugs were included as the test group and the control group for 1:1 matched case study; The target gene was detected by polymerase chain reaction （PCR） or in situ hybridization and correlation analysis was performed. Finally

combined with the clinical data of patients such as age

sex

dosage and duration of medication

we used multivariate logistic regression analysis to explore the relevant predictive factors affecting the occurrence of opioid constipation adverse reactions.

Results

CYP2D6

CYP3A5*3

ABCB1

and

OPRM1

were selected as target genes for detection; SNPStats genetic model analysis showed that

CYP3A5*3

（058rs776746

G）

OPRM1

（047rs1799971

G） polymorphisms were associated with opioid induced constipation

among which

CYP3A5*3

（058rs776746） GG

OPRM1

（047rs1799971） AA

AG were risk factors for opioid induced constipation. At the same time

combined with clinical data

logistic regression analysis showed that the duration of drug use

CYP3A5*3

and OPRM1 gene polymorphisms could all be used as predictors of constipation in patients using opioids.

Conclusion

CYP3A5*3

（058rs776746

G）

OPRM1

（047rs1799971

G） polymorphisms are associated with opioid induced constipation

which is expected to become a clinical predictor of adverse drug reactions of opioids

and more attention should be paid to the occurrence of severe constipation in patients who have been taking opioids for a long time.

关键词

Keywords

references

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