Clinical Pharmacogenetics: Results After Implementation of Preemptive Tests in Daily Routine

Area of Science:

• Pharmacogenetics
• Clinical Pharmacology
• Genomic Medicine

Background:

• Clinical implementation of pharmacogenetics (PGx) is limited due to infrastructure, education gaps, and lack of consensus on testing strategies and interpretation.
• Challenges include selecting appropriate genetic variants, choosing between single-gene and multi-gene panels, and translating genotypes into actionable therapeutic recommendations.

Purpose of the Study:

• To describe the implementation of pharmacogenetics in routine clinical practice at a single institution.
• To guide other centers by analyzing drug-gene interactions, genetic variants, and their clinical utility.
• To evaluate the necessity of specific genetic variant testing for drug prescribing.

Main Methods:

• Implementation of a pharmacogenetics program in daily clinical routine.
• Analysis of drug-gene interactions and genetic variants based on allelic, genotypic, and phenotypic frequencies.
• Performance of linkage disequilibrium and haplotype analyses to inform variant selection and interpretation.

Main Results:

• Pharmacogenetics testing was predominantly requested by the oncology department.
• Not all variants included in common pharmacogenetics panels demonstrated clinical utility in the study setting.
• Testing CYP2C19*17 before clopidogrel and CYP2C9*2 before siponimod was found to lack actionable therapeutic guidance.

Conclusions:

• The clinical utility of pharmacogenetics variants varies, and not all commonly tested variants are necessary for guiding therapy.
• Specific recommendations are made against routine testing of CYP2C19*17 for clopidogrel and CYP2C9*2 for siponimod.
• TPMT*3B testing may be considered primarily for confirming TPMT*3A due to linkage disequilibrium with TPMT*3C.