Akiko Nakamura

Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer

Background and Aim:  In Western countries, polymorphism of pro‐inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α with susceptibility to peptic ulcer diseases and gastric cancer in Japan.

Effects of interleukin-10 gene polymorphism on the development of gastric cancer and peptic ulcer in Japanese subjects

Background:  Anti‐inflammatory cytokines play an important role in downregulation of inflammation and the prevention of neoplastic disorders. Genetic variations of anti‐inflammatory cytokines are assumed to influence such responses. The aim of the present study was to clarify the association between the IL‐10 polymorphism, one of the representative anti‐inflammatory cytokines, and susceptibility to gastric cancer and peptic ulcer in Japan.

Influence of CYP2C19 Polymorphism and Helicobacter pylori Genotype Determined From Gastric Tissue Samples on Response to Triple Therapy for H pylori Infection

BACKGROUND & AIMS 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.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in japanese patients with Helicobacter pylori infection

Background : Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s).

Determination of mutations of the 23S rRNA gene of Helicobacter pylori by allele specific primer‐polymerase chain reaction method

Background and Aims:  Susceptibility to clarithromycin of Helicobacter pylori (H. pylori) is caused by single nucleotide polymorphisms (SNPs) of the 23SrRNA gene. Allele specific primer‐polymerase chain reaction (ASP‐PCR) is one of the methods for determining SNPs, which can measure SNPs easily within a short period by PCR amplification alone without digestion with restriction enzymes. The aim of the present study was to develop the ASP‐PCR assay for determining SNPs at positions 2142 and 2143 of the 23S rRNA gene of H. pylori.

Modified allele-specific primer–polymerase chain reaction method for analysis of susceptibility of Helicobacter pylori strains to clarithromycin

Background and Aim:  Most clarithromycin‐resistant strains of Helicobacter pylori have a mutation from adenine (A) to guanine (G) at position 2142 or 2143 of the 23S rRNA gene. Our aim in this study was to develop a polymerase chain reaction (PCR)‐based assay that could determine these mutations in a single reaction tube.

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status

Background : Famotidine increases Helicobacter pylori‐eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19.

Individualized treatment strategy for H. pylori infection based on the susceptibility of H. pylori to antibiotics and CYP2C19 genotypes

CYP2C19 genotype status of patients and the susceptibility of Helicobacter pylori (H. pylori) to clarithromycin (CAM) were major factors associated with the eradication rates of H. pylori by the triple therapy with a PPI, CAM, and amoxicillin (AMPC).