title: Decreased Activity and Genetic Polymorphisms of CYP2C19 in Behçet's Disease.
abstract: Behçet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes (CYPs) are responsible for various drug metabolism reactions as well as those of endogenous substances which may be associated with autoimmune disease susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to be down-regulated due to inflammation. In the same Turkish patients with BD, we investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27 healthy control volunteers. An HPLC method was used to determine plasma lansoprazole and its metabolite, 5-hydroxy lansoprazole, concentrations. The genotyping for CYP2C19 *2, *3 and *17 polymorphisms was made using PCR-RFLP. The median lansoprazole/5-hydroxy lansoprazole metabolic ratio (MR) in patients with BD was 2.6-fold higher as compared to the healthy control group (p = 0.001, 22.6 (1.3-26) and 8.8 (0.5-140) as median and range, respectively). The CYP2C19*17*17 genotype frequency was found to be significantly less in the BD group as compared to the healthy controls (1.7% versus 14.8% in controls, p = 0.01). Additionally, colchicine treatment did not affect the CYP2C19 enzyme activity in six patients (p = 0.43). In conclusion, the patients with BD had lower CYP2C19 enzyme activity and lower frequency of the CYP2C19*17 allele as compared to those of the healthy controls. Further studies are warranted on the mechanisms underlying this relation. This study should also be applied to other autoimmune diseases similarly characterized by local or systemic inflammation.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.|Department of Medical Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.
authors.forename: Mustafa Tugrul
authors.initials: MT
authors.lastname: Goktas
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Ragip Ozgur
authors.initials: RO
authors.lastname: Karaca
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Said
authors.initials: S
authors.lastname: Kalkisim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Lokman
authors.initials: L
authors.lastname: Cevik
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Kilic
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Akdogan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Melih O
authors.initials: MO
authors.lastname: Babaoglu
authors.affiliation: Department of Pharmacology, Faculty of Medicine, BAU International University, Batumi, Georgia.
authors.forename: Atilla
authors.initials: A
authors.lastname: Bozkurt
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology at Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Bertilsson
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Yasar
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001528:Behcet Syndrome / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D001711:Biotransformation; D016022:Case-Control Studies; D003078:Colchicine / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D064747:Lansoprazole / Q000097:blood; D010641:Phenotype; D011110:Polymorphism, Genetic; D013379:Substrate Specificity; D014421:Turkey
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000893:Anti-Inflammatory Agents; D064747:Lansoprazole; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; C498264:5-hydroxylansoprazole; D003078:Colchicine