CYP2C19 and CYP2D6 Genotypes and Metabolizer Status Distribution in a Bulgarian Psychiatric Cohort

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Psychiatric Genetics

Background:

• Cytochrome P450 enzymes CYP2D6 and CYP2C19 are crucial for metabolizing many psychiatric medications.
• Genetic variations (polymorphisms) in CYP2D6 and CYP2C19 genes lead to altered enzyme activity, affecting drug safety and efficacy.
• Population-specific frequencies of these genetic variations necessitate localized studies for clinical application.

Purpose of the Study:

• To investigate the frequencies of specific CYP2D6 and CYP2C19 genetic variants in a cohort of Bulgarian psychiatric patients.
• To determine the prevalence of different CYP2D6 and CYP2C19 metabolizer phenotypes within this population.
• To provide data supporting the implementation of precision medicine in Bulgarian psychiatric practice.

Main Methods:

• Genotyping analysis of CYP2C19 variants (*2, *4, *17) and CYP2D6 variants (*2, *3, *4, *5, *6, *10, *41).
• Analysis of 742 Bulgarian psychiatric patients, primarily diagnosed with depression and/or anxiety.
• Classification of patients into normal, intermediate, rapid, ultrarapid, and poor metabolizer categories based on their genotypes.

Main Results:

• 77% of the 742 patients (571 individuals) carried at least one variant affecting their metabolizer status.
• 48.6% of individuals were non-normal CYP2D6 metabolizers, predominantly intermediate (38.2%) and poor (6.6%) metabolizers.
• For CYP2C19, rapid (28.9%) and ultrarapid (5.5%) metabolizers were most common among non-normal metabolizers, with intermediate (23.8%) and poor (1.8%) metabolizers also identified.

Conclusions:

• This study provides critical genotype and phenotype data for CYP2D6 and CYP2C19 in Bulgarian psychiatric patients.
• The high prevalence of non-normal metabolizer phenotypes highlights the potential need for genotype-guided pharmacotherapy in this population.
• Findings support the integration of pharmacogenetic testing into Bulgarian psychiatric care for optimized treatment outcomes.