The Frequency of Cyp2c19 Genetic Polymorphisms In Russian Patients With Peptic Ulcer Treated With Proton Pump Inhibitors

Abstract

The Frequency oF cyP2c19 GeneTic PolymorPhisms in russiAn PATienTs WiTh PePTic ulcer TreATed WiTh ProTon PumP inhibiTors N.P. Denisenko; D.A. Sychev; Zh.M. Sizova; A.V. Grachev; and K.A. Velikolug Russian Medical Academy of Post-Graduate Education, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Moscow, Russia; SM-Clinic, Moscow, Russia; and Out-patient department No. 51 branch 3, Moscow, Russia Introduction: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcer, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultrarapid metabolism of proton pump inhibitors. Genetic polymorphism of CYP2C19 could be of clinical concern in the treatment of peptic ulcer with proton pump inhibitors. The aim of the study – to investigate the frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcer. Materials and Methods: The study involved 971 patients with peptic ulcer from the European part of Russia (Moscow), 428 male (44%) and 543 female (56%). The mean age was 44.6 ± 11.9 years (range 15–88 y). DNA isolated from blood samples was used for the analysis of CYP2C19 genetic polymorphisms (CYP2C19*2, *3, *17 alleles) by real-time polymerase chain reaction. Results: Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultrarapid metabolizers. Two hundred fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 – 0.140, CYP2C19*3 – 0.006, CYP2C19*17 – 0.274. Conclusion: There is a high frequency of CYP2C19 genotypes associated with modified response on proton pump inhibitors in Russian patients with peptic ulcer. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors.