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

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

白话标题:阿片类药物致便秘与基因多态性的相关性
作者: Jing YANG ¹ ; Xinyu ZHANG ² ; Lei ZHENG ³ ; Yuyao GUAN ³ ; Wenlai CHANG ³ ; Zhongkun LIN ³ ; Yahui ZHANG ⁴ ; Zheng FU ⁵
作者信息

1. Dept. of Pharmacy，Shandong Medical College，Jinan 250031，China;Dept. of Pharmacy，Shandong Provincial Third Hospital，Jinan 250031，China;School of Medical and Pharmaceutical Science，Ocean University of China，Shandong Qingdao 266000，China
2. School of Medical and Pharmaceutical Science，Ocean University of China，Shandong Qingdao 266000，China
3. Dept. of Pharmacy，Shandong Provincial Third Hospital，Jinan 250031，China
4. Dept. of Pharmacy，Shandong Provincial Hospital，Jinan 250031，China
5. Dept. of Pharmacy，Shandong Medical College，Jinan 250031，China
出版类型:Journal Article
关键字: opioids; gene polymorphism; adverse drug reactions; constipation; individualized medication
来源: China Pharmacy 2023;34(9):1104-1108
国家China
语言:Chinese
摘要: 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-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com 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 （P＜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 （P＜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.