Translational pharmacogenetics and risk management in the cardiovascular arena: CYP3A5*3 model for gene-based drug...

The clinical community is moving rapidly toward the prospective application of gene-based drug dosing. Specifically within the cardiovascular arena, the cytochrome P450 (CYP)3A5*3 allele may represent an optimal starting point. All CYP3A5*3 alleles contain an A6986G transition in intron 3, which reduces enzyme expression through the introduction of a premature stop codon. The current review explores four potential reasons why the clinical and scientific communities should consider including CYP3A5*3 in any panel of gene polymorphisms developed for the purpose of guiding cardiovascular pharmacotherapy: the CYP3A enzyme family metabolizes nearly half of all prescription drugs; the CYP3A enzyme family metabolizes several drugs utilized for primary and secondary risk reduction in the context of coronary artery disease; the CYP3A5*3 allele has been associated with differential outcomes related to lipid lowering therapy; and the CYP3A5*3 allele is highly prevalent in all populations studied to date.