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Polymorphisms in CYP2D6 may predict methamphetamine related heart failure.

M E Sutter¹, A Gaedigk, T E Albertson

¹Department of Emergency Medicine, University of California, Davis Medical Center, Sacramento, CA, USA. Mark.sutter@ucdmc.ucdavis.edu

Clinical Toxicology (Philadelphia, Pa.)

|July 17, 2013

Summary

Individuals with slower metabolism of methamphetamine (via CYP2D6 enzyme) showed a trend toward less heart failure. Extensive metabolizers may face a higher risk of developing methamphetamine-induced cardiomyopathy.

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Area of Science:

Pharmacogenetics
Cardiology
Toxicology

Background:

Methamphetamine (METH) use is linked to dilated cardiomyopathy.
The enzyme CYP2D6 is crucial for METH metabolism.
CYP2D6 exhibits genetic polymorphism, affecting drug processing.

Purpose of the Study:

To investigate the association between CYP2D6 gene polymorphisms and methamphetamine-induced cardiomyopathy.
To determine if variations in CYP2D6 activity influence the risk of developing METH-related heart conditions.

Main Methods:

A prospective case-control pilot study was conducted.
Cases had METH use, heart failure symptoms, and elevated BNP (>300 pg/ml).
Controls had METH use but no heart failure indicators (BNP <300 pg/ml).
Genotyping of CYP2D6 and echocardiography were performed.

Main Results:

19 cases and 37 controls were analyzed.
Poor CYP2D6 metabolizers showed a trend towards less heart failure compared to extensive metabolizers.
Extensive metabolizers had higher odds of developing dilated cardiomyopathy (OR: 2.33), though not statistically significant.
Cases exhibited significantly reduced ejection fractions (mean 18.6%) and 70% had dilated cardiomyopathy.

Conclusions:

A trend suggests individuals with lower CYP2D6 metabolic activity are less prone to METH-induced heart failure.
A potential increased risk for cardiomyopathy exists in extensive CYP2D6 metabolizers.
Further research is warranted to confirm the link between CYP2D6 polymorphisms and METH cardiotoxicity.