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阿片类药物不良反应与基因多态性相关性的研究:病例对照研究。

Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study.

机构信息

School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.

Department of Pharmacy, Shandong Medical College, Jinan, China.

出版信息

BMC Pharmacol Toxicol. 2023 Nov 21;24(1):64. doi: 10.1186/s40360-023-00708-4.

Abstract

OBJECTIVE

Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.

METHODS

Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.

RESULTS

Based on a database search and evidence-based medical data, we identified CYP2D610, CYP3A53, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.

CONCLUSION

Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

摘要

目的

阿片类药物引起的药物不良反应(ADR)存在个体差异。本研究旨在探讨与阿片类药物引起的 ADR 相关的基因多态性。

方法

对与阿片类药物引起的 ADR 相关的基因进行循证医学数据分析,选择靶基因。将 60 例服用阿片类药物(吗啡、可待因、羟考酮)后发生 ADR 的癌症疼痛患者作为实验组,60 例服用阿片类药物后未发生 ADR 的患者作为对照组。然后,采用聚合酶链反应(PCR)或原位杂交法检测靶基因。结合年龄、性别、用药剂量和疗程等临床资料,统计分析基因多态性对患者服用阿片类药物后 ADR 的影响。

结果

基于数据库检索和循证医学数据,确定 CYP2D610、CYP3A53、ABCB1 和 OPRM1 为检测的靶基因。实验组与对照组的基因型分布比较,差异无统计学意义(P>0.05)。然而,对 32 例服用羟考酮后发生 ADR 的患者和 32 例对照者进行比较,SPSS22.0 和 SNPStats 遗传模型显示,ABCB1(062rs1045642)CT 和 TT 基因型与 ADR 的发生相关(P<0.05):实验组 CT+TT 基因型总数为 29 例(90.62%),对照组 CT+TT 基因型为 11 例(34.37%)。

结论

ABCB1(062rs1045642)多态性与羟考酮引起的 ADR 相关,T 等位基因的 ADR 发生率较高。ABCB1 多态性有望成为羟考酮 ADR 的临床预测指标,应注意 ABCB1(062rs1045642)CT 和 TT 基因型患者发生严重 ADR 的情况。

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