CYP3A5

CYP3A5 is a gene encoding a member of the cytochrome P450 superfamily of enzymes. These enzymes are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. CYP3A5, specifically, belongs to the CYP3A subfamily, which is responsible for the metabolism of a wide variety of clinically important drugs.

The CYP3A5 gene is highly polymorphic, meaning it exhibits significant genetic variation among individuals and populations. This variation affects the expression and activity of the CYP3A5 enzyme, leading to interindividual differences in drug metabolism. Some individuals are extensive metabolizers (EMs), possessing high CYP3A5 activity, while others are poor metabolizers (PMs), with little to no CYP3A5 activity. Intermediate and rapid metabolizer phenotypes also exist.

The most common genetic variant influencing CYP3A5 expression is CYP3A53 (6986A>G; rs776742). The CYP3A51 allele generally results in high expression of the CYP3A5 enzyme, while the CYP3A53 allele results in aberrant splicing, leading to a non-functional protein and reduced or absent enzyme activity. Other variant alleles also exist but are less common.

The CYP3A5 enzyme is primarily expressed in the liver and intestine, although expression can also occur in other tissues. Its activity is induced by certain drugs and environmental factors.

Understanding an individual's CYP3A5 genotype can be crucial for personalizing drug therapy, as it can help predict how an individual will respond to certain medications metabolized by this enzyme. This information can inform dosage adjustments to maximize therapeutic efficacy and minimize the risk of adverse drug reactions. Testing for CYP3A5 polymorphisms is increasingly used in pharmacogenomics to guide drug selection and dosing.