Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis

Abstract

Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis.Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16.Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%).Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.

Relationships of Proton Pump Inhibitor‐Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study

“…9 Previous studies have shown that CYP2C19 genotypes are associated with clearance and plasma concentrations of PPIs, which contribute to the treatment success for H. pylori infection and erosive esophagitis. [10][11][12][13] In this way, individualizing PPI treatments based on CYP2C19 genotype is recommended to improve disease control in the field of gastroenterology. 9 In contrast, the relationship between CYP2C19 genetic polymorphism and adverse effects, including renal injury, remains uncertain.…”

“…According to the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 and PPI dosing, there is a substantial body of evidence linking CYP2C19 genotype with variability in plasma concentrations and efficacies of PPIs 9 . Previous studies have shown that CYP2C19 genotypes are associated with clearance and plasma concentrations of PPIs, which contribute to the treatment success for H. pylori infection and erosive esophagitis 10–13 . In this way, individualizing PPI treatments based on CYP2C19 genotype is recommended to improve disease control in the field of gastroenterology 9 .…”