The influence of genetic polymorphism of the CYP2C19 gene on the results of eradication therapy for Helicobacter pylori infection

Relevance. The decrease in the effectiveness of eradication therapy for Helicobacter pylori (H.pylori) infection is associated not only with an increase in resistance to antibacterial drugs, but also with the role of genetic polymorphism of CYP2C19 in the effectiveness of proton pump inhibitors (PPIs), which are mandatory components of all treatment regimens.

The aim of the study was to study the effect of CYP2C19 gene polymorphism on the efficacy of eradication therapy among patients in Novosibirsk.

Materials and methods. The study included 60 people with an indication for H. pylori eradication therapy: 25 men (41.7 %) and 35 women (58.3 %). The average age of the participants was 51.6±12.6 years, men were younger than women (47.6±11.6 years versus 54.4±12.7 years, p=0.04). Study participants were randomized by sex and age into two groups of 30 each depending on inclusion in a two-week eradication regimen as a proton pump inhibitor (PPI) of rabeprazole (group 1) or lansoprazole (Lancid® Kit, group 2). A clinical and laboratory study was conducted, the status of H. pylori infection was determined by two or more standardized diagnostic tests. Genetic polymorphism of CYP2C19*2 (*3, *17) gene was investigated using the reagent kit for detection of allelic variants in the human CYP2C19 gene – «GenTest CYP2C19» (HOMOTEK, Russia) by real-time PCR.

Results. Variants of the CYP2C19 *2 gene with a minor allele affecting the decrease in enzyme activity (slow metabolizers) were detected in 21.7 % of cases. The frequency of the CYP2C19*2 minor allele was 13.1 %. In more than half of the cases (53.3 %), a heterozygous variant of CYP2C19*17 with increased enzyme function was detected, and in another 10.0 % of cases, a homozygous variant with ultrafast enzyme function, which confirms the predominance of fast metabolizers among Caucasians. The frequency of the CYP2C19*17 minor allele was 26.8 %. The efficacy of eradication therapy was higher in the lansoprazole (LancidKit) group and amounted to 90 %, with no significant difference between the groups. Non-effective eradication (positive stool antigen test for H. pylori) was less common in those with slow metabolism (CYP2C19 * 2 minor allele variant) compared to the normal variant (CYP2C19 * 1) in the general group (22.2 vs. 77.8 %, p=0.03) and in the rabeprazole group (16.7 vs 83.3 %, p=0.04), with no significant difference for lansoprazole (Lancid® Kit). Cases of ineffective eradication were more frequent compared to effective treatment with rapid metabolism (variants of the CYP2C19*17 genotype with a minor allele) in the general group (88.9 vs. 11.1 %, p=0.004), in the group with rabeprazole (83.3 vs. 16.7 %, p=0.04) and in all 3 cases in the group with lansoprazole p= 0.07)

Conclusion. Thus, in patients from Novosibirsk, the frequency of minor alleles affecting metabolic rate corresponds to the frequencies typical of Caucasians. A positive H. pylori antigen test in the stool after treatment, indicating ineffective eradication, was less common in individuals with slow metabolism compared to those with normal metabolism in the overall group and in the group treated with rabeprazole, with no significant difference for lansoprazole (Lansid® Kit). In rapid metabolizers, ineffective therapy was observed more often in comparison with effective treatment, both in the general and in the compared groups. To obtain unambiguous conclusions on the effectiveness of PPIs in the eradication of H. pylori infection, depending on the genetic polymorphism of CYP2C19, it is necessary to give.

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