[28] Allele A (23% global frequency) is associated with decreased dose of warfarin as compared to the allele G (77% global frequency). Two nonsynonymous polymorphisms, rs1799853 (c.430C > T, p.Arg144Cys) and rs1057910 (c.1075A > C, p.Ile359Leu), define the CYP2C9*2 and CYP2C9*3 alleles, respectively (https://www.pharmvar.org/gene/CYP2C9, accessed 31 Jan 2018). A wide variation exists in how this gene metabolizes these drugs. A similar range of CYP2C9 alleles is found among African-Americans from both North and South America, although CYP2C9*2 and *3 are also relatively common among African-Americans [54]. As discussed, S warfarin is also subject to metabolism at other positions by other CYP isoforms [6]. CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 accounted for less than 2.5% in these populations. Cytochrome P450 2C9 (CYP2C9) and CYP3A4 are major enzymes involved in the 11-hydroxylation and the 8-(or 7-) hydroxylation, respectively, of the cannabinoids by human hepatic microsomes (Watanabe et al., 2007). [15] In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms. This decrease coincides with about a 20% reduction in warfarin-dose requirements with the CYP2C9∗8 allele [78]. Recent data suggest that CYP2C9*8 occurs in South Indians [56]. Inhibitors of CYP2C9 can be classified by their potency, such as: CYP2C9 attacks various long-chain polyunsaturated fatty acids at their double (i.e. Information gained so far on the impact of CYP2C9 and warfarin has been used to develop CPIC guidelines to guide warfarin therapy in patients (Johnson et al., 2011). Warfarin, a racemic mixture of the enantiomers, S- and R-warfarin, is the most widely prescribed anticoagulant agent. [8] 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 pages). Cytochrome P450 2C9 is an important drug metabolizing enzyme and accounts for ca.18% of cytochrome P450 protein content in the human microsomes [112]. of the *1/*1 genotype, are designated extensive metabolizers (EM), or normal metabolizers. These result in decreased enzymatic activity. Consequently, it has been reported that phenytoin maintenance doses are about 30% lower in heterozygous carriers of these CYP2C9 alleles and 30%–50% lower in homozygous carriers than in noncarriers. The CPIC guideline for pharmacogenetics-guided warfarin dosing and its annotations (https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/) provide detailed instructions on how to use pharmacogenetic algorithms for warfarin dosing (Johnson et al., 2017). The CYP2C9 allele in poor metabolizers has a frequency of approximately 2-6% in white populations (22). The allele frequencies of CYP2C9*2 and CYP2C9*3 generally tend to be higher in white populations than Asian populations (Xie et al., 2002). CYP2C9∗2 is frequent among Caucasians with approximately 1% of the population being homozygous carriers and 22% heterozygous. Some people have CYP2C19 enzyme that does not work well (Intermediate and Poor Metabolizers) while others have CYP2C19 enzyme that works better than average (Rapid and Ultrarapid Metabolizers). CYP2C9*2 is also relatively common in admixed Americans (7%), South Asians (5%), and Africans (2%) but very rare in East Asians, while CYP2C9*3 is remarkably common in South Asians (11%) and fairly common in East Asians and Americans (3%–4%). In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. Phenytoin, a hydantoin anticonvulasant, is another drug with a narrow therapeutic index and individual dose requirements. The CYP2C9 ∗5, ∗6, and ∗11 alleles also occur almost exclusively in African Americans but at much lower frequencies than the ∗8 allele. The CYP2C9*2 and CYP2C9*3 alleles are much less prevalent among Asians and African-Americans. faster losartan metabolism. This enzyme also assists in metabolizing other drugs such as ibuprofen, which reduces inflammation. Both CYP2C9*2 and CYP2C9*3 are associated with impaired clearance of phenytoin. The first algorithm developed on a sufficient patient population was published 10 years ago by Gage et al. Patients heterozygous for CYP2C9*2 demonstrated stronger reduction of diastolic and systolic blood pressure compared to patients homozygous for CYP2C9*1 (wild type). It was reported that polymorphism of CYP2C9 as well as of CYP2C19 contributes to variability in phenytoin pharmacokinetics. Fluorouracil: DPYD: intermediate or poor metabolizer Accordingly, the respective CPIC guideline recommends a 25%–50% reduction of phenytoin starting maintenance dose in decreased-function CYP2C9 allele carriers, with subsequent maintenance doses adjusted based on therapeutic drug monitoring or response (Caudle et al., 2014). Caucasians are fast metabolizers… Sufficient number of studies has provided comparable results general! ~ 18 % of people of Caucasian descent antiinflammatory drugs ( e.g play a role prediction! Ile359Leu ) are more sensitive to adverse events upon administration of drugs metabolized by CYP2C9 about a greater... 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