CYP2C9 enzyme activity is involved in the metabolism of substances related to colorectal cancer (CRC), and it is functionally linked to a genetic polymorphism. Two allelic variants of the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, differ from wild-type CYP2C9*1 by single amino acid substitutions. These mutated alleles encode enzymes with altered properties that are associated with impaired meta...

Losartan, an angiotensin II receptor antagonist, is oxidized by hepatic cytochromes P450 to an active carboxylic acid metabolite, E-3174. The aim of the present investigation was to study the contribution of CYP2C9 and CYP3A4 in losartan oxidation in vitro and to evaluate the role of CYP2C9 polymorphism. Kinetic properties of different genetic CYP2C9 variants were compared both in a yeast expre...

BACKGROUND Warfarin has been widely used for the prevention and treatment of thromboembolism. Warfarin therapy depends on interaction between physiological, environmental, and genetic factors. Vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) enzyme conjointly determine the warfarin maintenance dose. The prevalence of CYP2C9 and VKORC1 variants varies among ethnic groups. Th...

We examined the distribution of major allelic variants of CYP2C9 and CYP2C19 in the Mongolian population of China and compared it with that of other populations. The polymorphisms of CYP2C9 (including the CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles) and CYP2C19 (including the CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles) were analyzed in 280 healthy unrelated Chinese Mongolian subjects, using a PCR-R...

OBJECTIVE Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs). CYP2C9-derived EETs elicit endothelial cell proliferation and angiogenesis, but the signaling pathways involved are incompletely understood. Because cyclooxygenase-2 (COX-2) is involved in angiogenesis, we determined whether a link exists between CYP2C9 and COX-2 expression. METHODS A...

CYP2C9 wild-type protein has been shown to exhibit atypical kinetic profiles of metabolism that may affect in vitro-in vivo predictions made during the drug development process. Previous work suggests a substrate-dependent effect of polymorphic variants of CYP2C9 on the rate of metabolism; however, it is hypothesized that these active site amino acid changes will affect the kinetic profile of a...

Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirem...

Polymorphisms in cytochrome P450 enzymes can significantly alter the rate of drug metabolism, as well as the extent of drug-drug interactions. Individuals who homozygotically express the CYP2C9*3 allele (I359L) of CYP2C9 exhibit ∼70 to 80% reductions in the oral clearance of drugs metabolized through this pathway; the reduction in clearance is ∼40 to 50% for heterozygotic individuals. Although ...

BACKGROUND CYP2C9*3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers. We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients. MATERIAL/METHODS The study was prospective, without any interventions to standard procedures of hypolipidemi...