The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

Abstract

DA Sychev,1,2 NP Denisenko,1,2 ZM Sizova,2 AV Grachev,3 KA Velikolug4 1Russian Medical Academy of Post-Graduate Education, 2I.M. Sechenov First Moscow State Medical University, 3SM-Clinic, 4Out-patient department Number 51 branch 3, Moscow, Russia Introduction: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. Aim: To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. Methods: We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15–88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G>A (CYP2C19*2, rs4244285), CYP2C19 636 G>A (CYP2C19*3, rs4986893) and CYP2C19 -806 C>T (CYP2C19*17, rs12248560) were evaluated using 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 and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and 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 to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors. Keywords: CYP2C19, proton pump inhibitors, peptic ulcer, Russian