Pharmacogenomics-Based Tailor-Made Strategy for Eradication of Helicobacter Pylori

Current treatment strategies for the eradication of H. pylori include a proton pump inhibitor (PPI) and one or two anti-bacterial agents, such as amoxicillin, clarithromycin, and metronidazole.

PPIs, such as lansoprazole and omeprazole, are mainly metabolized in the liver by a genetically determined enzyme, S-mephenytoin 4'-hydroxylase (CYP2C19). Plasma concentrations of PPIs and their activity for acid inhibition depend to a significant extent on the genetic differences in the activity of this enzyme. The acid inhibition attained by the standard dose of a PPI is sometimes therapeutically insufficient in individuals with the rapid extensive metabolizer (RM) genotype of CYP2C19, whereas that in individuals with poor metabolizer (PM) genotype of CYP2C19 is in most cases clinically sufficient. We have reported that the CYP2C19 genotype status is one of the determinants of H. pylori eradication therapy. In the triple therapy with a PPI, amoxicillin, and clarithromycin, bacterial susceptibility to clarithromycin as well as the CYP2C19 genotype status was significantly related to eradication rates of H. pylori. Therefore, the tailored treatment based on these two factors is expected to increase the eradication rates of the initial therapy.

Interestingly, both of CYP2C19 genotypes and bacterial susceptibility to clarithromycin can be measured by the genetic test of the single nucleotide polymorphisms (SNPs) of the CYP2C19 gene and the 23S rRNA gene of H. pylori, respectively. We have recently developed the inexpensive and reliable high-throughput method for measurement of such SNPs by the invader assay. Polymorphisms of CYP2C19 of patients and mutations of 23S rRNA of H. pylori associated with susceptibility to clarithromycin can be detected from the gastric tissue samples infected with H. pylori, such as the gastric tissue sample already used for rapid urease test (RUT).

Then, we treat H. pylori-positive patients by the tailored regimen based on genotypes of CYP2C19 of patients and 23S rRNA of H. pylori or the standard regimen and test the therapeutic efficacy of this pharmacogenomics-based tailored strategy in a prospective manner.

Patients were randomly assigned to the standard or tailored regimen group with the use of a computer-generated randomization list based on a blocked randomization method.