[7] CYP2C9 is a crucial cytochrome P450 enzyme, which plays a significant role in the metabolism, by oxidation, of both xenobiotic and endogenous compounds.

[10] Animal models and a limited number of human studies implicate these epoxides in reducing hypertension; protecting against myocardial infarction and other insults to the heart; promoting the growth and metastasis of certain cancers; inhibiting inflammation; stimulating blood vessel formation; and possessing a variety of actions on neural tissues including modulating neurohormone release and blocking pain perception (see epoxyeicosatrienoic acid and epoxygenase).

[16] In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms.

Especially for CYP2C9 substrates such as warfarin and phenytoin, diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses.

[17][18] Information about how human genetic variation of CYP2C9 affects response to medications can be found in databases such PharmGKB,[19] Clinical Pharmacogenetics Implementation Consortium (CPIC).

[20] The label CYP2C9*1 is assigned by the Pharmacogene Variation Consortium (PharmVar) to the most commonly observed human gene variant.

[21] Other relevant variants are cataloged by PharmVar under consecutive numbers, which are written after an asterisk (star) character to form an allele label.

[28] CYP2C9*3 reflects an Ile359-Leu (I359L) change in the amino acid sequence,[29] and also has reduced catalytic activity compared with the wild type (CYP2C9*1) for substrates other than warfarin.

This recommendation was based on their well-established functional effects on CYP2C9 activity and drug response availability of reference materials, and their appreciable allele frequencies in major ethnic groups.

[32] This variant is caused by a T269C mutation in the CYP2C9 gene which in turn results in the substitution of leucine at position-90 with proline (L90P) at the product enzyme protein.

[31] However, this variant is not included in the tier 1 recommendations of the PGx Working Group because of its very low multiethnic minor allele frequency and a lack of currently available reference materials.

[9] Animal model studies implicate these epoxides in regulating: hypertension, myocardial infarction and other insults to the heart, the growth of various cancers, inflammation, blood vessel formation, and pain perception; limited studies suggest but have not proven that these epoxides may function similarly in humans (see Epoxyeicosatrienoic acid and Epoxygenase).