Abstract

Background

Investigations proposed that genetic polymorphisms within proteins in methadone pharmacokinetic and pharmacodynamics are critical factors in determination of methadone dose in methadone maintenance therapy (MMT).

Objective

This study aimed to assess the associations between two polymorphisms, CYP3A4 (rs2740574) and OPRM1 (rs1799971), with dose of methadone in Iranian patients undergoing MMT.

Methods

A total of 124 Iranian male subjects aged 18–65 years old who were confirmed to be addicted by the addiction diagnostic tests and underwent MMT were assessed. Patients were divided into three groups of low (less than 40 mg/day), moderate (more than 40 mg/day and less than 110 mg/day) and high (more than 110 mg/day) methadone dose consumption. DNAs of included patients were extracted from their blood samples and were assessed for CYP3A4 and OPRM1 polymorphisms.

Results

Results showed that there was no significant association between the studied polymorphisms and methadone dose in Iranian addicted patients underwent MMT (P > 0.05).

Conclusions

CYP3A4 and OPRM1 single variations cannot explain variability in methadone dosage in MMT. Studying the interactions of more genetic factors in larger samples may elucidate factors influencing the required dose of methadone and better individualized therapy.

中文翻译：

---

在接受美沙酮维持治疗的伊朗患者中，OPRM1 和 CYP3A4 与美沙酮剂量的相关性

摘要

背景

研究表明，美沙酮药代动力学和药效学中蛋白质的遗传多态性是确定美沙酮维持治疗 (MMT) 中美沙酮剂量的关键因素。

客观的

本研究旨在评估两种多态性CYP3A4 (rs2740574) 和OPRM1 (rs1799971) 与接受 MMT 的伊朗患者的美沙酮剂量之间的关联。

方法

共评估了 124 名 18-65 岁的伊朗男性受试者，他们被成瘾诊断测试确认为上瘾并接受了 MMT。患者被分为低（低于 40 毫克/天）、中度（超过 40 毫克/天和低于 110 毫克/天）和高（超过 110 毫克/天）的美沙酮剂量消耗三组。从他们的血液样本中提取了纳入患者的 DNA，并评估了CYP3A4和OPRM1多态性。

结果

结果表明，在接受 MMT 的伊朗成瘾患者中，研究的多态性与美沙酮剂量之间没有显着关联（P > 0.05）。

结论

CYP3A4和OPRM1单一变异不能解释 MMT 中美沙酮剂量的变异性。在更大的样本中研究更多遗传因素的相互作用可能会阐明影响美沙酮所需剂量和更好的个体化治疗的因素。