Pharmacogenet Genomics 2010 Apr;20(4):277-81
Center for Pharmacogenomics at Washington University, St Louis, Missouri, USA.
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Clin Chem Lab Med 2004 Jan;42(1):72-8
Clinical Institute of Chemistry, School of Medicine, Sestre milosrdnice University Hospital, Zagreb, Croatia.
CYP2C9, an isoform of the cytochrome P450 enzyme, is involved in the metabolism of most of the drugs of choice for the treatment of thromboembolic disorders. Functional polymorphism is associated with two variant alleles (alleles *2 and *3) encoding CYP2C9 enzymes with a potentially different catalytic activity. The aim of the study was to determine the frequency of the CYP2C9 polymorphism in a representative sample of the Croatian population (n = 177) and to assess the association between the CYP2C9 polymorphism and the warfarin dose in patients with thromboembolism (n = 181). Read More
Curr Drug Metab 2009 Sep;10(7):781-834
Department of Pediatrics, Guangdong Women and Children's Hospital, 13 Guangyuanxi Road, Guangzhou 510010, China.
Human cytochrome P450 2C9 (CYP2C9) accounts for approximately 20% of total hepatic CYP content and metabolizes approximately 15% clinically used drugs including S-warfarin, tolbutamide, phenytoin, losartan, diclofenac, and celecoxib. To date, there are at least 33 variants of CYP2C9 (*1B through to *34) being identified. CYP2C9*2 and CYP2C9*3 differ from the wild-type CYP2C9*1 by a single point mutation: CYP2C9*2 is characterised by a 430C>T exchange in exon 3 resulting in an Arg144Cys amino acid substitution, whereas CYP2C9*3 shows an exchange of 1075A>C in exon 7 causing an Ile359Leu substitution in the catalytic site of the enzyme. Read More
Pharmacogenet Genomics 2007 Jul;17(7):473-9
Department of Epidemiology, Erasmus MC, Rotterdam, Inspectorate for Health Care, The Hague, The Netherlands.
Objective: The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction.
Methods: We investigated whether the variant alleles CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was associated with an increased risk of myocardial infarction in 2210 men and 3534 women from the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years or older.
Results: In women, the use of CYP2C9 substrates or inhibitors was significantly associated with incident myocardial infarction with a hazard ratio of 2. Read More
Annu Rev Pharmacol Toxicol 2005 ;45:477-94
Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA.
CYP2C9 is a major cytochrome P450 enzyme that is involved in the metabolic clearance of a wide variety of therapeutic agents, including nonsteroidal antiinflammatories, oral anticoagulants, and oral hypoglycemics. Disruption of CYP2C9 activity by metabolic inhibition or pharmacogenetic variability underlies many of the adverse drug reactions that are associated with the enzyme. CYP2C9 is also the first human P450 to be crystallized, and the structural basis for its substrate and inhibitor selectivity is becoming increasingly clear. Read More