Recombinant Human Cytochrome P450 2C9 (CYP2C9)

1. Molecular dynamics simulations performed for the active species of the enzyme (heme in the Compound I state), in the apo or substrate-bound state, and binding energy analyses gave insights into altered protein structure and dynamics involved in the defective drug metabolism of human allelic variant CYP2C9*30 (A477T). PMID: 29746595
2. Lower expression of CYP2C9 was associated with better overall survival and disease-free survival in Hepatocellular carcinoma tumor samples. PMID: 29974848
3. A significant association between CYP2C9*3 and phenytoin-induced Stevens-Johnson syndrome was identified, especially in a Thai population (Meta-Analysis) PMID: 29274302
4. In this study, we showed that patients with VKORC1-1639GA and CYP2C9*1/*1 alleles have lower sensitivity for warfarin than those with VKORC1-1639AA and CYP2C9*1/*1 alleles. PMID: 29781049
5. Enzyme phenotyping with correlation analysis confirmed the predominant role of CYP2C9 in the biotransformation of siponimod and demonstrated the functional consequence of CYP2C9 genetic polymorphisms and fluconazole on siponimod metabolism. PMID: 29273968
6. Comparisons of pharmacokinetics of 25 substrates CYP2C9, CYP2C19, or CYP2D6 in healthy Chinese and European subjects (classified with same enzyme activity) suggest that, for most substrates, limited interethnic pharmacokinetic differences exist (according to the databases used in this study). (CYP2C19 = cytochrome P450 family 2 subfamily C member 19; CYP2D6 = cytochrome P450 family 2 subfamily D member 6) PMID: 29181698
7. genetic association studies in population in Scotland: data suggest, in type 2 diabetes treated with sulfonylureas, 2 SNPs in CYP2C9 (CYP2C9*2, R144C, rs1799853; CYP2C9*3, I359L, rs1057910) are associated with drug-induced hypoglycemia; an SNP in POR (POR*28, A503V, rs1057868) is associated with better response to sulfonylureas. (CYP2C9 = cytochrome P450 family 2 subfamily C member 9; POR = cytochrome p450 oxidoreductase) PMID: 28656666
8. The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. PMID: 27503578
9. The final regression models for White and Black patients (Fig. 1) included age, weight, prosthetic valves, amiodarone use, CYP2C9*3, and VKORC1 3673 G>A genotypes as covariates, whereas possession of CYP2C9*2 and simvastatin use were retained in the final model for White, but not Black patients. PMID: 28263279
10. Our results further support a minor contribution of CYP2C9 genetic variability toward steady-state endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes. PMID: 28877533
11. CYP2C9 genetic variation was associated with long-term overall mortality and non-major bleeding in elderly patients treated with vitamin K antagonists. PMID: 28834238
12. Until the age of 19, weight has a far greater effect on Vitamin K antagonist dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 polymorphisms play a significant role. PMID: 28284562
13. CYP2C9*3 did show significant effect on warfarin dose requirement PMID: 27313202
14. Two SNPs in CYP2C9, rs2153628 and rs1799853 are associated with response to indomethacin for the treatment patent ductus arteriosus. PMID: 28609430
15. the carriership of individual C and T alleles in the case of CYP2C9*2 gene, as well as A and C for CYP2C9*3 is not a predictor of antiretroviral drug-induced liver injury. PMID: 29787666
16. Genetic polymorphisms in CYP2C9 cause significant interindividual variability in the metabolism of its substrates. This study estimated the coefficient of variation (CV) for the intrinsic hepatic clearance of tolbutamide by CYP2C9 for each CYP2C9 genotype using previously reported area under the blood concentration curve (AUC) and oral clearance (CLoral) values in a Monte Carlo simulation with a dispersion model. PMID: 28435143
17. These results suggest that genetic polymorphisms of CYP2C9 enzymes result in the production of varying levels of biologically active JWH-018 metabolites in some individuals, offering a mechanistic explanation for the diverse clinical toxicity often observed following JWH-018 abuse. PMID: 29522717
18. Studied the association of CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms on warfarin dose requirements in patients post cardiac valve surgery. Found age and presence of CYP2C9 *2 allele significantly affect the daily dosage of warfarin during initiation of warfarin therapy after cardiac valve replacement surgery. PMID: 29182754
19. CYP2C9 mutations had a significant impact on 2-propyl-4-pentenoic acid concentration PMID: 28315807
20. Angiotensin II receptor blockers exhibit different degrees of inhibition of the metabolism of arachidonic acid by recombinant CYP2C9, CYP2J2 and liver microsomes. PMID: 28374982
21. analysis of VKORC1 AA-CYP2C9*1*1 genotypes reveals dosing algorithms for vitamin K antagonists PMID: 28063245
22. To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. CYP2C9*2 and *3 allele variants modify benzodiazepine-related fall risk. Those using benzodiazepines and having reduced CYP2C9 enzyme activity based on their genotype are at increased fall risk. PMID: 27889507
23. In an Indian population of children with epilepsy on phenytoin monotherapy, CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants. PMID: 27179628
24. The genotype distributions of the CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose. PMID: 28872889
25. CYP2C9*2 and CYP2C9*3 genetic polymorphisms are associated with reduced S-warfarin oral clearance in healthy subjects PMID: 27878474
26. Case Report: time course of CYP2C9 deinduction appeared to be delayed compared to CYP3A after discontinuation of rifampicin therapy. PMID: 28157069
27. Data suggest that SNPs in CYP2C9 (*3, I359L; *30, A477T) that reduce catalytic activity of CYP2C9 also alter interaction with antihypertensive drug losartan; I359L substitution located far from active site remarkably alters residue side chains near active site and access channel, whereas the T477 substitution illustrates hydrogen-bonding interaction with reoriented side chain of Q214. PMID: 28972767
28. SNP rs4918758 of CYP2C9 showed a suggestive association with decreased risk of coronary heart disease. PMID: 28687336
29. CYP2C9*31075AC genotype with combined alcohol and nevirapine usage indicated a risk for development of antiretroviral-associated hepatotoxicity PMID: 28370504
30. CYP2C9 polymorphisms showed no effect on PC doses. Similar findings were observed in the initiation phase of PC therapy. High complications rates under PC therapy were observed particularly at the beginning. PMID: 26984978
31. Genetic variants of CYP2C9/VKORC1 and age are significant determinants of the maintenance dose of warfarin in patients with atrial fibrillation/valve replacement. PMID: 27117036
32. CYP2C9*3 polymorphism genotype and allele frequency were not statistically different between the case and control Ankylosing Spondylitis groups (P>0.05). the efficacy of NSAID in treatment of AS and COX-2 gene -1290A/G and -1195G/A polymorphism were associated (all P<0.05), but it is not associated with CYP2C9 *3 polymorphism (all P>0.05). PMID: 28403136
33. polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol PMID: 27826892
34. Possession of CYP2C9*2 and/or CYP2C9*3 allele variants is associated with lower time of international normalized ratio (INR) in the therapeutic range (TTR) values and warfarin dose variations in aortic valve replacement patients, the latter affected also by VKORC1 c.-1693G>A polymorphism PMID: 27511999
35. Three SNPs (CYP2C9 *2, *3 and VKORC1 c.-1639G > A) were genotyped by electrochemical detection using a sandwich-type format that included a 3' short thiol capture probe and a 5' ferrocene-labeled signal probe. PMID: 28083852
36. Two subjects with CYP2C9PM genotype both showed markedly higher AUC, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypesTwo subjects with CYP2C9PM genotype both showed markedly higher AUC0-infinity, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes PMID: 27864660
37. CYP2C9 IVS8-109 T carriers showed significantly higher dose-corrected phenoytoin blood concentrations and this allele was found in a higher frequency in epileptic patients with supratherapeutic phenytoin levels. PMID: 26122019
38. Med25, a variable member of the Mediator complex, is a coactivator of ligand-activated ERalpha that interacts with ERalpha through its C-terminal LXXLL motif after BPA exposure, and is functionally involved in BPA-induced transcriptional regulation of CYP2C9 expression and enzyme activity. PMID: 27273787
39. Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes. PMID: 28033245
40. Review/Meta-analysis: CYP2C9 gene polymorphism was significantly associated with decreased warfarin maintenance dose requirements in pediatric patients. PMID: 27661060
41. The intrinsic clearance (Vmax/Km) values of all variants, with the exception of CYP2C9*2, CYP2C9*11, CYP2C9*23, CYP2C9*29, CYP2C9*34, CYP2C9*38, CYP2C9*44, CYP2C9*46 and CYP2C9*48, were significantly different from CYP2C9*1. CYP2C9*27, *40, *41, *47, *49, *51, *53, *54, *56 and N418T variant exhibited markedly larger values than CYP2C9*1. PMID: 27163851
42. Report roles for CYP3A4 and CYP2C9 in sequential two-step bioactivation of diclofenac to reactive p-benzoquinone imines. PMID: 27130197
43. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians. PMID: 27938396
44. Cyp2C9 genetic polymorphisms significantly affected the plasma concentrations of zafirlukast. PMID: 27377818
45. The high frequency of CYP2C9*3 and the absence of CYP2C9*2 in Jahais suggest that genetic drift may be occurring in this ethnic group. PMID: 26402341
46. VKORC1-CYP2C9 interaction can affect warfarin stable dosage. PMID: 25187307
47. Results show a statistically significant association between CYP2C9*3 polymorphism and phenytoin-related Stevens-Johnson syndrome. PMID: 26928377
48. P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR*28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects PMID: 26669712
49. VKORC1S1639 GG and the wild type CYP2C9*1*1 genotypes are associated with the high-dose requirement for warfarin therapy. PMID: 24978953
50. Patients with variant CYP2C9 are at increased risk for cyclophosphamide-induced leukopenia but may have a better chance to respond to treatment. PMID: 26894931

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HGNC: 2623

OMIM: 601130

KEGG: hsa:1559

STRING: 9606.ENSP00000260682

UniGene: Hs.282624