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

Eur J Clin Pharmacol. 2015 Oct;71(10):1223-8. doi: 10.1007/s00228-015-1899-7. Epub 2015 Aug 2.


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.

Keywords: Behçet’s disease; CYP2C9; Colchicine; Genotype; Losartan metabolism; Phenotype; Turkish population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Behcet Syndrome / drug therapy
  • Behcet Syndrome / genetics*
  • Chromatography, High Pressure Liquid
  • Colchicine / therapeutic use
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP2C9 / metabolism*
  • Cytokines / metabolism
  • Down-Regulation
  • Female
  • Genotype
  • Humans
  • Imidazoles / urine
  • Inflammation / metabolism
  • Losartan / pharmacokinetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Tetrazoles / urine
  • Turkey


  • Cytokines
  • Imidazoles
  • Tetrazoles
  • Cytochrome P-450 CYP2C9
  • losartan carboxylic acid
  • Losartan
  • Colchicine