Study on the correlation between opioid-induced constipation and gene polymorphism

YANG Jing; ZHANG Xinyu; ZHENG Lei; GUAN Yuyao; CHANG Wenlai; LIN Zhongkun; ZHANG Yahui; FU Zheng

doi:10.6039/j.issn.1001-0408.2023.09.15

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Study on the correlation between opioid-induced constipation and gene polymorphism

更新时间：2023-11-06

- Study on the correlation between opioid-induced constipation and gene polymorphism
- ZHONGGUO YAOFANG Vol. 34, Issue 9, Pages: 1104-1108(2023)
- 作者机构：
  
  1.山东医学高等专科学校药学系，济南　250031
  2.山东省立第三医院药学部，济南　250031
  3.中国海洋大学医药学院，山东青岛　266000
  4.山东省立医院药学部，济南　250031
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.09.15
  CLC： R971
- Published：15 May 2023，
  
  Received：20 November 2022，
  
  Revised：26 February 2023，
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杨静,张新宇,郑磊等.阿片类药物致便秘与基因多态性的相关性 ^Δ[J].中国药房,2023,34(09):1104-1108.

YANG Jing,ZHANG Xinyu,ZHENG Lei,et al.Study on the correlation between opioid-induced constipation and gene polymorphism[J].ZHONGGUO YAOFANG,2023,34(09):1104-1108.
杨静,张新宇,郑磊等.阿片类药物致便秘与基因多态性的相关性 ^Δ[J].中国药房,2023,34(09):1104-1108. DOI： 10.6039/j.issn.1001-0408.2023.09.15.

YANG Jing,ZHANG Xinyu,ZHENG Lei,et al.Study on the correlation between opioid-induced constipation and gene polymorphism[J].ZHONGGUO YAOFANG,2023,34(09):1104-1108. DOI： 10.6039/j.issn.1001-0408.2023.09.15.

摘要

目的

探讨基因多态性对阿片类药物致便秘的影响。

方法

首先通过检索指南、数据库及循证医学资料等筛选出与阿片类药物致便秘相关的目标基因，随后纳入100例接受阿片类药物进行镇痛治疗的癌痛患者，并根据用药后是否出现便秘分为试验组和对照组，每组各50例。利用PCR或荧光原位杂交法对目标基因进行检测；使用SNPStats程序进行Hardy-Weinberg平衡检验、基因多态性与阿片类药物致便秘的相关性分析，采用多因素Logistic回归分析阿片类药物致便秘发生的相关预测因素，绘制受试者工作特征（ROC）曲线分析各预测因素在预测阿片类药物致便秘方面的效能。

结果

筛选出的目标基因有

CYP2D6

、

CYP3A5*3

、

ABCB1

、

OPRM1

。基因型检测结果显示，

CYP2D6

（rs1065852、rs1135822、rs16947、rs28371725、rs28371735）、

CYP3A5*3

（058rs776746）、

ABCB1

（062rs1045642）、

OPRM1

（047rs1799971）等位基因频率分布均符合Hardy-Weinberg平衡检验。相关性分析结果显示，试验组患者

CYP3A5*3

（058rs776746，A＞G）中的GG、AG型，

OPRM1

（047rs1799971，A＞G）中的AA、AG型占比显著高于对照组（

＜0.05）。多因素Logistic回归分析结果显示，用药时间及

CYP3A5*3、OPRM1

基因多态性可作为患者发生阿片类药物致便秘的预测因素（

＜0.05）。ROC曲线分析结果显示，用药时间及

CYP3A5*3

、

OPRM1

基因多态性的ROC曲线下面积分别为0.648、0.640、0.670，最佳截断值分别为124.0、0.5、0.5。

结论

CYP3A5*3

（058rs776746，A＞G）GG、AG型，

OPRM1

（047rs1799971，A＞G）AA、AG型与阿片类药物致便秘具有相关性，且上述基因型可能是患者使用阿片类药物致便秘的预测因素，同时还需要关注用药时间较长患者的便秘发生情况。

Abstract

OBJECTIVE

To investigate the effect of gene polymorphism on opioid-induced constipation.

METHODS

The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation.

RESULTS

CYP2D6， CYP3A5*3， ABCB1

and

OPRM1

were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of

CYP2D6

（rs1065852， rs1135822， rs16947， rs28371725， rs28371735），

CYP3A5*3

（058rs776746），

ABCB1

（062rs1045642），

OPRM1

（047rs1799971） alleles were consistent with Hardy-Weinberg balance test. The correlation analysis results showed that the proportion of genotype GG and AG in

CYP3A5*3

（058rs776746， A＞G） and genotype AA and AG in

OPRM1

（047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （

＜0.05）. Multivariate Logistic regression analysis showed that medication duration，

CYP3A5*3

and

OPRM1

gene polymorphism could be used as predictors of opioid-induced constipation in patients （

＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and

CYP3A5*3

，

OPRM1

gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively.

CONCLUSIONS

Genotype GG and AG in

CYP3A5*3

（058rs776746，A＞G） and genotype AA and AG in

OPRM1

（047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

关键词

阿片类药物基因多态性药物不良反应便秘个体化用药

Keywords

gene polymorphismadverse drug reactionsconstipationindividualized medication

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