Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients.

OBJECTIVE: Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles (CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients. METHODS: A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 - success, and group 2 - failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17). RESULTS: Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 (p=0.060) for *1, 15.4 versus 5.3 (p=0.015) for *2, and 28.2 versus 25.5 (p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication (p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015). CONCLUSION: Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole.

Effect of CYP2C19 and MDR1 polymorphisms on cure rate in patients with acid-related disorders with Helicobacter pylori infection.

A proton pump inhibitor (PPI) plus two antibiotics (amoxicillin and either clarithromycin or metronidazole) are recommended for treatment of acid-related disorders with Helicobacter pylori (H. pylori) infection. The aim of this pharmacogenetic study was to evaluate the efficacy of triple therapy with PPIs on eradication of H. pylori infection in relation to cytochrome P450 2C19 (CYP2C19) and P-glycoprotein (MDR1) gene polymorphisms. The retrospective study involved 70 Polish Caucasian patients with H. pylori infection, diagnosed and treated with one of the two different triple therapy regimens [omeprazole, amoxicillin, and clarithromycin (OAC) or pantoprazole, amoxicillin, and metronidazole (PAM)]. Using genomic DNA, CYP2C19 (*2 and *3) and C3435T MDR1 alleles were determined by means of polymerase chain reaction-restriction fragment length polymorphism assays. A significantly higher prevalence (P<0.05) of heterozygous extensive metabolizers (hetEM) with CYP2C19*1/*2 genotype (32.4% versus 8.3%) and homozygous with 3435TT MDR1 genotype (38.2% versus 13.9%) was found in patients cured after the first cycle of triple therapy than in patients with failure of eradication after the first cycle. CYP2C19*1/*2 and 3435TT MDR1 genotypes as well as PAM regimen of treatment were also predictive of successful eradication of H. pylori infection after the first cycle of triple therapy at univariate/multivariate logistic regression analysis. This pharmacogenetic study on the influence of different CYP2C19 and C3435T MDR1 genotypes on H. pylori eradication suggests that CYP2C19 and MDR1 polymorphisms may be independent predictable determinants of the efficacy of triple therapy including PPI. The PAM regimen of treatment seems to be more effective after the first cycle of the therapy than the OAC regimen.

The -590 IL-4 promoter polymorphism in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to evaluate the -590 IL-4 promoter polymorphism in patients with RA and its association with disease activity and severity. We enrolled 94 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the polymorphism at position -590 of the promoter of the IL-4 gene. The distribution of IL-4 genotypes in RA patients did not differ from control subjects. Nevertheless, the active form of RA was more frequently diagnosed in patients with T allele (genotypes CT and TT) as compared with homozygous CC patients. Moreover, in carriers of the T allele, parameters of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. We suggest that the IL-4 -590 promoter polymorphism may be a genetic risk factor for RA severity.