Distribution of Cytochrome P450 Metabolizer Status and Allelic Variants in Individuals with Mental Health Disorders in Ontario,Canada: Répartition du statut métabolique du cytochrome P450 et des variantes alléliques chez les personnes atteintes de problèmes de santé mentale en Ontario,au Canada

Abstract

Introduction

Drug metabolism is primarily carried out by the cytochrome P450 (CYP) family of enzymes in the liver. Based on an individual's diplotype, they can be classified into poor (PM), intermediate (IM), normal (NM), rapid (RM) or ultrarapid (UM) metabolizers. Here, we show the distribution of allele frequency and metabolizer status across ancestries for CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A4 and CYP1A2 in a cohort from Ontario, Canada.

Methods

Patients currently taking or starting a psychotropic drug (N = 8,280) were enrolled. Patients self-reported their ancestry, and DNA was analysed for the CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A4 and CYP1A2 genes using a commercial pharmacogenetic test and metabolizer status was assigned using ClinPGx as a reference.

Results

The cohort was primarily of European ancestry (70%), followed by individuals with mixed ancestry (9.3%). The combined frequency of PMs and UMs, representing the extremes of enzyme activity, was highest for CYP2C19 and CYP2D6, with this frequency being approximately 8% for each enzyme. The frequency varied considerably by ancestry, with up to 24% of individuals of Caribbean descent being CYP2C19 PMs or UMs, for example, compared to only 7% among those of Latin, Central and South American ancestry. Of the entire sample, only 5.1% were NMs across all enzymes, meaning 94.9% of individuals had a non-NM status and would benefit from pharmacogenetic testing.

Conclusion

Overall, this study provides a useful reference for variations in the CYP family of genes in the population of Ontario, Canada.