OPRM1 and CYP3A4 association with methadone dose in Iranian patients undergoing methadone maintenance therapy

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.

Keywords:

• rs1799971
• CYP3A4*1B
• methadone
• opiate replacement therapy
• Iran

Acknowledgments

We appreciate the support of the Shahid Beheshti University of Medical Sciences Vice Chancellor for Research and the Neuroscience Research Center of Shahid Beheshti University of Medical Sciences to carry out this research project.

Declaration of interest statement

None declared.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Authors’ contribution

Ahmad Akbari, Ali Kheradmand, Sareh Asadi, and Abolhassan Ahmadiani participated in the study design, the conception of research questions, literature review and the drafting of the paper. Ahmad Akbari contributed in acquisition of clinical data and Marzieh Sina performed the lab works. All authors contributed in manuscript editing and review.

Additional information

Funding

This work was supported by a grant from Neuroscience Research Center, Shahid Beheshti University of Medical Sciences.