Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?...Cytochrome P450 2C9
Background: We previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease? Aim: This study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subj...
| Published in: | European Journal of Clinical Pharmacology Vol. 71; no. 10; pp. 1223 - 1229 |
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| Main Authors: | , , , , , , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Springer Nature
Oct2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=109345398&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109345398 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Oct2015 vid: 71 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 109345398 109345398 109345398 10.1007/s00228-015-1899-7 109345398 ppf: 1223 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?...Cytochrome P450 2C9 aug: au: Goktaş, Mustafa Hatta, Fazleen Karaca, Ozgur Kalkisim, Said Kilic, Levent Akdogan, Ali Babaoglu, Melih Bozkurt, Atilla Helldén, Anders Bertilsson, Leif Yasar, Umit affil: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara Turkey sug: subj: Oxidoreductases Analysis Behcet's Syndrome Physiopathology Inflammation Genotype Phenotype Behcet's Syndrome Complications Human Turkiye Polymerase Chain Reaction Losartan Administration and Dosage Descriptive Statistics T-Tests Colchicine Therapeutic Use Behcet's Syndrome Drug Therapy Cytokines Losartan Metabolism Fisher's Exact Test Chi Square Test Data Analysis Software Male Female Adult Middle Age Aged Polymorphism, Genetic Confidence Intervals Funding Source Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Male Female ab: Background: We previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease? Aim: This study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subjects. As the occurrence of BD is high in Turkey, all subjects were recruited from this country. Methods: Genotyping of CYP2C9 was performed using standard PCR-RFLP and allele-specific PCR methods. Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Quantitation was performed by HPLC. Results: The frequency of CYP2C9*2 and *3 was not significantly different between the Behçet's disease patients (12.5 and 8.7 %) and the healthy subjects (8.9 and 8.2 %). The geometric mean losartan MR was higher in the 52 patients (1.75) than in the 96 healthy subjects (1.02) ( p = 0.002; t-test). Within the genotypes *1/*1, there was a significant difference of MR between patients and healthy subjects ( P = 0.006). All but three of the Behçet's disease patients were treated with colchicine. In nine subsequent patients, we found no significant effect of 2 weeks of treatment with colchicine on the CYP2C9 MR. Conclusion: Contrary to expectation, the CYP2C9 activity was lower in Turkish BD patients compared to healthy subjects. As this seems not to be due to colchicine treatment, our hypothesis is that inflammation related to BD might have caused the down-regulation of the CYP2C9 activity due to immune cytokine reactions. The ultra-rapid metabolism of CYP2C9 substrate drugs in the Swedish patient was not due to her BD. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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