Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes.

ABSTRACT:

Background

Variations in pharmacogenes that regulate drug absorption, distribution, metabolism, and excretion (ADME) contribute to approximately 20-30% of interindividual differences in drug response. While many common variants are successfully utilized in clinical settings to predict individual drug responses, a significant portion of the genetic basis underlying this variability remains unidentified. This includes rare variants, which are estimated to account for 4-6% of drug response variability.

Results

To comprehensively elucidate the functional consequences and molecular mechanisms of rare variants, we conducted in vitro enzyme expression studies combined with in silico structure-function analyses. We selected 11 rare variants in the CYP2C19 and CYP2D6 genes identified

SUBMITTER: Johansson I 

PROVIDER: S-EPMC12117788 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature