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Lower CYP2C9 activity in Turkish patients with Behçet’s disease compared to healthy subjects: a down-regulation due to inflammation?

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

Support wasgranted by Hacettepe University Scientific Research Projects Coordination Unit (HU.09.D06.101.005).

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Author notes

  1. Mustafa Tugrul Goktaş

    Present address: Department of Medical Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Mustafa Tugrul Goktaş, Ozgur Karaca, Said Kalkisim, Melih O. Babaoglu, Atilla Bozkurt & Umit Yasar

  2. Department of Laboratory Medicine, Division of Clinical Pharmacology at Karolinska Institutet, Karolinska University Hospital, Huddinge, 14186, Stockholm, Sweden

    Fazleen Hatta, Anders Helldén & Leif Bertilsson

  3. Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia

    Fazleen Hatta

  4. Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Levent Kilic & Ali Akdogan

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  1. Mustafa Tugrul Goktaş
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Correspondence to Fazleen Hatta.

Additional information

Mustafa Tugrul Goktaş and Fazleen Hatta contributed equally to this work.

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Goktaş, M.T., Hatta, F., Karaca, O. et al. Lower CYP2C9 activity in Turkish patients with Behçet’s disease compared to healthy subjects: a down-regulation due to inflammation?. Eur J Clin Pharmacol 71, 1223–1228 (2015). https://doi.org/10.1007/s00228-015-1899-7

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