Cytochrome P450 2C9 Genotyping

Cytochrome P450 2C9 (CYP2C9) is a drug-metabolizing enzyme involved in the metabolism of several clinically important drugs, including warfarin, phenytoin, siponimod and some nonsteroidal anti-inflammatories. Individuals with some variant CYP2C9 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by CYP2C9. CYP2C9 genotype information can be utilized to predict CYP2C9 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP2C9. For example, CYP2C9 poor metabolizers mat experience increased concentrations of a drug with a reduced or absent therapeutic response. Warfarin metabolism is reduced by 30-50% by *2 and 90% by *3 alleles: individuals with at least one copy of *2 or *3 have an increased risk of bleeding compared to individuals without *2 or *3. In these instances, a lower warfarin maintenance dose may be required or alternative drugs may be considered.

Variation in the CYP2C9 gene can result in normal (NM), intermediate (IM) and poor (PM) drug-metabolizing phenotypes. In general, relative to the *1 allele (normal function), *2, *5, *8 and *11 alleles have decreased function, while *3, *6 and *13 alleles have no function.