Pharmacogenomics
Genetic polymorphism exists for CYP2C9 expression because the CYP2C9 gene is highly polymorphic. More than 50 single nucleotide polymorphisms (SNPs) have been described in the regulatory and coding regions of the CYP2C9 gene, some of them are associated with reduced enzyme activity compared with wild type in vitro.
Multiple in vivo studies also show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. 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.
Allele frequencies(%) of CYP2C9 polymorphism
| African-American | Black-African | Pygmy | Asian | Caucasian | |
|---|---|---|---|---|---|
| CYP2C9*2 | 2.9 | 0-4.3 | 0 | 0-0.1 | 8-19 |
| CYP2C9*3 | 2.0 | 0-2.3 | 0 | 1.1-3.6 | 3.3-16.2 |
| CYP2C9*5 | 0-1.7 | 0.8-1.8 | ND | 0 | 0 |
| CYP2C9*6 | 0.6 | 2.7 | ND | 0 | 0 |
| CYP2C9*7 | 0 | 0 | 6 | 0 | 0 |
| CYP2C9*8 | 1.9 | 8.6 | 4 | 0 | 0 |
| CYP2C9*9 | 13 | 15.7 | 22 | 0 | 0.3 |
| CYP2C9*11 | 1.4-1.8 | 2.7 | 6 | 0 | 0.4-1.0 |
| CYP2C9*13 | ND | ND | ND | 0.5-0.6 | ND |
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