title: Influence of CYP2C19 polymorphism and Helicobacter pylori genotype determined from gastric tissue samples on response to triple therapy for H pylori infection.
abstract: OBJECTIVE
  The relationship between single nucleotide polymorphisms (SNPs) and clinical outcomes has been intensively studied. We intended to determine SNPs of CYP2C19 and 23S rRNA of Helicobacter pylori by using rapid urease test (RUT)-positive gastric mucosal samples.
  
  
  METHODS
  One hundred thirty-nine patients with H pylori -positive results based on RUT completed 1-week treatment with lansoprazole 30 mg twice a day, clarithromycin 200 mg 3 times daily, and amoxicillin 500 mg 3 times daily. SNPs from adenine to guanine at positions 2142 and 2143 of 23S rRNA of H pylori (A2142G and A2143G) and SNPs from guanine to adenine at positions 681 in exon 5 (* 2 ) and 636 in exon 4 (* 3 ) of CYP2C19 were determined by the serial invasive signal amplification reaction assay by using DNAs extracted from gastric tissue samples already used for RUT. Minimum inhibitory concentrations of clarithromycin for H pylori were determined by culture test. CYP2C19 genotypes were classified into the rapid metabolizer (* 1 /* 1 ), intermediate metabolizer (* 1 /* 2 or * 1 /* 3 ), and poor metabolizer (* 2 /* 2 , * 2 /* 3 , or * 3 /* 3 ) groups.
  
  
  RESULTS
  H pylori strains with A2142G or A2143G mutation had higher minimum inhibitory concentrations for clarithromycin. Cure rates in rapid, intermediate, and poor metabolizer groups were 57.8% (95% confidence interval, 42.1%-72.4%), 88.2% (78.1%-94.8%), and 92.3% (74.9%-99.1%), respectively ( P < .001). Cure rates in strains with and without A2142G or A2143G mutation were 48.3% (29.4%-67.5%) and 87.3% (79.5%-92.7%), respectively ( P < .001).
  
  
  CONCLUSIONS
  SNPs of CYP2C19 and 23S rRNA of H pylori using RUT-positive gastric mucosal samples could be predictable determinants for H pylori eradication by triple therapy.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuta@hama-med.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sagehashi
authors.forename: Naohito
authors.initials: N
authors.lastname: Shirai
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodaira
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kenmotsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagano
authors.forename: Tohru
authors.initials: T
authors.lastname: Egashira
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.forename: Masao
authors.initials: M
authors.lastname: Yoneyama
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D017291:Clarithromycin / Q000627:therapeutic use; D015169:Colony Count, Microbial; D065731:Cytochrome P-450 CYP2C19; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D005756:Gastritis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012329:RNA, Bacterial / Q000187:drug effects / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000187:drug effects / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000890:Anti-Infective Agents; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D064747:Lansoprazole; D000658:Amoxicillin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin; D009853:Omeprazole