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Decreased Activity and Genetic Polymorphisms of CYP 2C19 in Behçet's Disease
Author(s) -
Goktas Mustafa Tugrul,
Karaca Ragip Ozgur,
Kalkisim Said,
Cevik Lokman,
Kilic Levent,
Akdogan Ali,
Babaoglu Melih O.,
Bozkurt Atilla,
Bertilsson Leif,
Yasar Umit
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12710
Subject(s) - lansoprazole , cyp2c19 , medicine , metabolite , pharmacology , genotype , cyp3a4 , genotyping , gastroenterology , cytochrome p450 , endocrinology , chemistry , metabolism , biochemistry , omeprazole , gene
Behçet's disease ( BD ) is a systemic autoimmune disorder. Cytochrome P450 enzymes ( CYP s) 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 , CYP 2C9 seems to be down‐regulated due to inflammation. In the same Turkish patients with BD , we investigated whether also CYP 2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP 2C19 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 CYP 2C19 *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 CYP 2C19*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 CYP 2C19 enzyme activity in six patients ( p = 0.43). In conclusion, the patients with BD had lower CYP 2C19 enzyme activity and lower frequency of the CYP 2C19*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.