Pharmacogenetic study of methadone treatment for heroin addiction: associations between drug-metabolizing gene polymorphisms and treatment efficacy.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-01-01 DOI:10.1097/FPC.0000000000000450

Yen-Jung Chen, Ju-Ting Lu, Chun-Wei Huang, Wei-Hsin Wu, Kuei-Fang Lee, Hsin-Tzu Liu, Lawrence Shih-Hsin Wu

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引用次数: 2

Abstract

Objectives: Opioid dependence is currently one of the most serious problems affecting the social norms and public health system. Methadone maintenance therapy (MMT) is being widely used in treating heroin-dependent patients. The mechanism of methadone metabolism and disposition has been shown to involve cytochrome P450 (CYP450) and P-glycoprotein. The aim of this study was to explore the relationships among genetic polymorphisms, BMI and effective dose of methadone used in MMT within a northern Taiwan cohort.

Methods: One hundred heroin-dependent patients were enrolled in the study. The clinical data gathered included methadone dose, sex and BMI. DNA was collected from the oral swab of the participants to analyze the relevant alleles.

Results: An effective methadone dose correlated with sex, BMI and the presence of ABCB1 2677GG (rs2032582) and CYP2B6 516GG (rs374527). Furthermore, the CYP2B6 516GG homozygote was related to a higher average dose of methadone (GG: 68.50 ± 32.43; GT: 52.28 ± 25.75; TT: 44.44 ± 29.64; P < 0.02), whereas the ABCB1 2677GG homozygote was related to a lower dose (GG: 51.09 ± 20.83; GT: 69.65 ± 37.51; TT: 62.52 ± 30.44; P < 0.05). We examined the predictive effect of polymorphisms combined with sex and BMI on methadone dose by conducting multiple linear regressions. Our data predicted the average dose of methadone in approximately 30% of heroin-dependent patients.

Conclusion: The interactions between genetic polymorphisms and clinical features proved useful in identifying the effective dose of MMT for heroin-dependent patients in Taiwan more precisely.

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美沙酮治疗海洛因成瘾的药物遗传学研究:药物代谢基因多态性与治疗效果的关系。

目的:阿片类药物依赖是目前影响社会规范和公共卫生系统的最严重问题之一。美沙酮维持疗法(MMT)被广泛应用于海洛因依赖患者的治疗。美沙酮代谢和处置的机制已被证明涉及细胞色素P450 (CYP450)和p糖蛋白。摘要本研究旨在探讨台湾北部人群在MMT治疗中，遗传多态性、BMI与美沙酮有效剂量之间的关系。方法:选取100例海洛因依赖患者作为研究对象。收集的临床数据包括美沙酮剂量、性别和身体质量指数。从参与者的口腔拭子中收集DNA以分析相关等位基因。结果:美沙酮有效剂量与性别、BMI、ABCB1 2677GG (rs2032582)和CYP2B6 516GG (rs374527)存在相关。此外，CYP2B6 516GG纯合子与较高的平均美沙酮剂量相关(GG: 68.50±32.43;Gt: 52.28±25.75;Tt: 44.44±29.64;P < 0.02)，而ABCB1 2677GG纯合子与低剂量相关(GG: 51.09±20.83;Gt: 69.65±37.51;Tt: 62.52±30.44;P < 0.05)。我们通过多元线性回归检验了多态性、性别和BMI对美沙酮剂量的预测作用。我们的数据预测了大约30%的海洛因依赖患者的平均剂量美沙酮。结论:遗传多态性与临床特征之间的相互作用有助于更准确地确定台湾海洛因依赖患者MMT的有效剂量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.