[Comparison of two cases of type 2 autoimmune pancreatitis].

We describe two cases of type 2 autoimmune pancreatitis (AIP). A 39-year-old man presented to our hospital with complaints of epigastric and back pain. Pancreatic enzyme levels were elevated, but serum levels of immunoglobulins G and G4 (IgG and IgG4) were normal. Computed tomography (CT) showed diffuse pancreatic enlargement, and endoscopic retrograde pancreatography revealed diffuse narrowing of the pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed granulocytic epithelial lesions and very few IgG4-positive cells. Colonoscopy revealed ulcerative colitis. Type 2 AIP was diagnosed, and 5-aminosalicylic acid (5-ASA) and prednisolone were administered. The clinical course has since been favorable, and the prednisolone dose is currently being reduced. A 47-year-old woman presented to our hospital with complaints of bloody stools. Colonoscopy revealed ulcerative colitis. CT depicted diffuse pancreatic enlargement with a capsule-like rim. Pancreatic enzyme levels were elevated, but serum levels of IgG and IgG4 were normal. On magnetic resonance cholangiopancreatography, the pancreatic duct could not be delineated. No pathological findings of type 2 AIP were obtained on EUS-FNA. Type 2 AIP was suspected, and 5-ASA and steroid enemas were administered. To date, recurrence has not been observed, and 5-ASA management continues. The two cases differed with regard to sex of patient, clinical course, pathological findings, and treatment.

Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese.

INTRODUCTION: The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power. METHODS: Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers. RESULTS: Median pH with rabeprazole was 5.4 (3.3-7.5), which was significantly greater than with either omeprazole [4.4 (2.1-7.3)] or lansoprazole [4.8 (3.5-6.4)] (both P < 0.05). Median 24-h pH differed among the different CYP2C19 genotypes in all three PPIs. In CYP2C19 extensive metabolizers (EMs), the genotype that is refractory to PPI treatment, median pH with omeprazole, lansoprazole, and rabeprazole was 3.8 (2.1-4.4), 4.5 (3.5-5.3) and 4.8 (3.3-7.5), respectively. DISCUSSION: Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.

Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19.

The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.

Role of renin-angiotensin system in gastric oncogenesis.

The renin-angiotensin system (RAS) plays an important role not only in homeostasis but also in carcinogenesis. Recent epidemiological studies suggest that hypertensive patients with upregulated systemic RAS functions are at a significantly increased risk for the subsequent development of cancers with poor outcomes, and moreover that RAS inhibitors reduce tumor development, progression, and metastasis. Notably, Helicobacter pylori infection, one of the major predictors of gastric carcinogenesis, generally leads to RAS component overexpression, as exemplified by that of angiotensin I, angiotensin II, angiotensin I converting enzyme and angiotensin II receptor. Gastric mucosal RAS expression gradually increases with time after H. pylori infection with respect to the severity of inflammatory cell infiltration. Gastric carcinogenic potential is therefore considered to relate to RAS component expression levels and activities. This hypothesis is supported by findings that RAS genotypic variation can lead to high component expression levels (e.g. angiotensin I converting enzyme, chymase and angiotensinogen), and thereby increase the risk of development of gastric cancer. Thus, the RAS may be potently associated with the pathogenesis of H. pylori-related gastric carcinogenesis, and RAS inhibitors may provide tools for specifically preventing this disease.

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P < .05). Medians of pH 3 holding time and mean 24-hour pH values with the lansoprazole regimen were significantly higher than those with famotidine (P < .05). No significant differences in MLS were observed among the different CYP2C19 genotype groups in any of the treatment regimens. In this 7-day study, lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

The dual therapy with 4 times daily dosing of rabeprazole and amoxicillin as the 3rd rescue regimen for eradication of H. pylori.

BACKGROUNDS/AIMS: Most of patients who are refractory to usual standard eradication therapies for H. pylori infection have rapid metabolizer genotype of CYP2C19 and are infected with resistant strains to several antimicrobial agents. However, most of H. pylori strains are sensitive to amoxicillin. We tested whether dual therapy with the 4 times daily dosing of rabeprazole and amoxicillin was effective as the 3rd rescue regimen for eradication of H. pylori. METHODOLOGY: 49 patients who failed in eradication of H. pylori after two (1st: proton pump inhibitor (PPI)/amoxicillin/clarithromycin and 2nd: PPI/amoxicillin/metronidazole) were enrolled to the study. They were treated with rabeprazole 10 mg q.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks. At 4 weeks after the treatment, they underwent the [13C]-urea breath test. When the result of [13C]-urea breath test was negative, they underwent the endoscopy and the successful eradication was confirmed by rapid urease test. RESULTS: All patients completed the treatment. The eradication rate was 87.8% (43/49) (95% CI = 75.2%-95.4%). No undesirable severe adverse events were observed during the study period. CONCLUSIONS: The dual therapy with 4 times daily dosing of rabeprazole and amoxicillin is well tolerated and effective as the 3rd rescue regimen for eradication of H. pylori.

Relationship between low-dose aspirin-induced gastric mucosal injury and intragastric pH in healthy volunteers.

BACKGROUND AND AIMS: Gastric acid plays an important role in the pathogenesis of gastric mucosal lesions. We investigated whether aspirin-induced gastric mucosal injury might have any association with the intragastric pH. MATERIALS AND METHODS: Fifteen healthy, Helicobacter pylori-negative volunteers randomly underwent the four different 7-day regimens: (1) aspirin 100 mg, (2) rabeprazole 10 mg, (3) aspirin 100 mg + rabeprazole 10 mg, and (4) aspirin 100 mg + rabeprazole 40 mg. Gastric mucosal injury based on the modified Lanza score (MLS), 24-h intragastric pH, and histopathology of gastric mucosa were evaluated prior to the start and on day 7 of each regimen. RESULTS: The median MLSs were 0 in the baseline and the rabeprazole 10 mg regimen. The median MLS in the aspirin regimen was 3, while those in both aspirin + rabeprazole 10 mg and aspirin + rabeprazole 40 mg regimens were 0. Rabeprazole significantly prevented the gastric mucosal injury by aspirin (P = 0.001 for rabeprazole 10 mg and P = 0.005 for rabeprazole 40 mg). The MLSs were negatively correlated with the 24-h intragastric pH (P = -0.711, < 0.001), whereas aspirin had no effect on the intragastric pH. Aspirin expanded the mean diameter of the microvessels of the gastric mucosa, which, in turn, was negatively correlated with the intragastric pH. CONCLUSIONS: Aspirin might induce gastric mucosal injury by affecting the mucosal microvessels in an acid-dependent manner. Sustained maintenance of the intragastric pH at an elevated value is necessary to prevent gastric mucosal damage induced by aspirin.

CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole.

BACKGROUND/AIMS: Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI. METHODS: We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS: In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19-0.87, P = 0.021) and 0.19 (95%CI: 0.05-0.69, P = 0.011). CONCLUSION: When the dose of lansoprazole is decreased, the RM genotype of CYP2C19 appears to be a risk factor for symptomatic recurrence of GERD. The CYP2C19 genotyping test would be useful for determining the optimal dose of a PPI for maintenance therapy of GERD.

Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects.

BACKGROUND AND AIMS: The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects. METHODS: Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n = 5), C/T (n = 5), and T/T (n = 5). Lansoprazole 30 mg was administered orally for 15 days. The intragastric pH and plasma lansoprazole levels were determined on days 1 and 15. RESULTS: On day 1, the mean C(max) of lansoprazole in the T/T group was significantly higher than that in the C/C or C/T groups (T/T 1,248, C/C 618, C/T 607 ng/ml; P = 0.038). On day 15, similar MDR1 genotype-dependent differences were observed in the C(max) of lansoprazole, although smaller than the differences observed on day 1. In contrast, the intragastric pH attained after lansoprazole administration did not differ among MDR1 genotype groups on either day 1 or day 15. CONCLUSION: Although the sample size was small, our study demonstrated that the MDR1 C3435T polymorphism influenced the pharmacokinetics, but not the pharmacodynamics (i.e., intragastric pH), of lansoprazole in rapid metabolizers of CYP2C19.

Maintenance time of sedative effects after an intravenous infusion of diazepam: a guide for endoscopy using diazepam.

AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP) 2C19 genotypes after an infusion regimen of diazepam commonly used for gastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical flicker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P<0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.

Serum pepsinogens as an early diagnostic marker of H. pylori eradication.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) eradication increases the serum pepsinogen I/ pepsinogen II ratio and the percentage change in pepsinogen I/pepsinogen II ratios is a useful marker of H. pylori eradication. We studied whether the pepsinogen method could be an early diagnostic marker of H. pylori eradication even in patients persistently treated with a proton pump inhibitor. METHODOLOGY: Sixty-two H. pylori-positive patients underwent H. pylori-eradication therapy, followed by treatment with a proton pump inhibitor to cure ulcers. Serum levels of pepsinogen I and pepsinogen II were measured before, at the end of, and at 4 weeks after the eradication therapy. The cut-off values of percentage changes in pepsinogen I/pepsinogen II ratios for the diagnosis of eradication of H. pylori were set in proportion to pepsinogen I/pepsinogen II ratios before eradication in accordance with a previous report. RESULTS: Using the results of 13C-urea breath test as the standard, the sensitivity, specificity and validity of the pepsinogen method were 100.0%, 89.8% and 90.3%, respectively, at 4 weeks after eradication therapy. CONCLUSION: The percentage change in serum pepsinogen I/pepsinogen II ratios is useful as an early diagnostic marker for judgment of H. pylori eradication irrespective of proton pump inhibitor treatment.

MDR1 C3435T polymorphism has no influence on developing Helicobacter pylori infection-related gastric cancer and peptic ulcer in Japanese.

AIMS: P-glycoprotein, the gene product of multidrug-resistant transporter-1 (MDR1), confers multidrug resistance against antineoplastic agents but also affects the kinetic disposition of some drugs and carcinogens. MDR1 C3435T polymorphism influences the development of colon cancer and adult acute myeloid leukemia by the association with transporting carcinogen. The aim of this study was to clarify the association of MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcers in patients with Japanese H. pylori infection. MAIN METHODS: We assessed the MDR1 C3435T polymorphism in H. pylori-positive gastritis alone patients (n=150), gastric cancer (n=292), gastric ulcer (n=215), and duodenal ulcer (n=163) and H. pylori-negative subjects (n=168) as control by a PCR-based method. KEY FINDINGS: No significant difference existed in frequencies of MDR1 C3435T polymorphisms between H. pylori-negative controls and H. pylori-positive gastritis alone patients. Moreover, MDR1-3435 T allele carriage didn't affect the risk of gastric cancer or peptic ulcer development. The age- and sex-adjusted odds ratios (ORs) of MDR1 3435 T allele carriers relative to the C/C genotype group for gastric cancer, gastric ulcer and duodenal ulcer risk were 0.96 (95%CI: 0.56-1.66), 1.16 (95%CI: 0.72-1.84) and 1.00 (95%CI: 0.61-1.62), respectively. SIGNIFICANCE: In this preliminary data, the association with MDR1 C3435T polymorphism and risk for developing H. pylori-related gastric cancer and peptic ulcer in Japanese was low. P-glycoprotein might not be involved in the carcinogenesis of H. pylori-related gastric cancer.

It is possible to classify non-erosive reflux disease (NERD) patients into endoscopically normal groups and minimal change groups by subjective symptoms and responsiveness to rabeprazole -- a report from a study with Japanese patients.

The hypothesis that non-erosive reflux disease (NERD) patients comprise various subgroups is gaining popularity. This study was conducted to investigate the possibility of categorizing NERD patients according to symptom types and response to acid-suppressive drug rabeprazole (RPZ) 10 mg/day. NERD patients were classified as grade N (endoscopically normal), M (minimal change), or erosive GERD, and answered a 51-item, yes-or-no questionnaire pre and post-treatment. Compared to erosive GERD, clear differences existed in pretreatment prevalence of symptoms and responsiveness to RPZ in grades N and M; the results suggested stomachaches (especially at night) were significant symptoms in grade N and dysmotility-like symptoms like bloated stomach were significant in grade M while gastroesophageal reflux symptoms were significant in erosive GERD. Clinical significance of classifying NERD was indicated from different symptoms and responsiveness to PPI.

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. METHODS: We designed the forward primer FP2143G and the reverse primer RP2142G, which specifically anneal with the 2143G- and 2142G-mutated sequences, respectively, of the 23S rRNA gene of H. pylori. We also designed the forward primer FP-1 and reverse primer RP-1 upstream and downstream from the positions 2142 and 2143, respectively, to distinguish the wild-type A2142G and A2143G mutations from each other by amplicon sizes. DNA was extracted from 292 gastric tissue samples positive for rapid urease test, and the DNA underwent the PCR reaction. The results were compared with minimum inhibitory concentrations (MIC) for clarithromycin. RESULTS: Helicobacter pylori strains with A2142G, A2143G and wild type could be distinguished by amplicon sizes by a single PCR reaction. The genotyping results were correlated well with the MIC values for clarithromycin. The median MIC for clarithromycin of the wild-type strains was <0.015 microg/mL. Those of strains with 2142G or 2143G were > or =1.0 microg/mL. CONCLUSION: Our new PCR-based assay for 23S rRNA mutations of H. pylori is a useful method for detecting clarithromycin-resistant strains of H. pylori easily.

CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor.

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are metabolized by CYP2C19 in the liver. There are genetic differences in the activity of this enzyme. Genotypes of CYP2C19 are classified into three groups, rapid metabolizer (RM: *1/*1), intermediate metabolizer (IM: *1/*X) and poor metabolizer (PM: *X/*X) (*1 and 'X' represent the wild-type and mutant allele, respectively). The pharmacokinetics and pharmacodynamics of PPIs differ among three different CYP2C19 genotype groups. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotypic differences in pharmacokinetics and pharmacodynamics of PPIs influence the healing and eradication rates for the gastro-esophageal reflux disease and Helicobacter pylori infection by PPI-based regimens. Recently, the CYP2C19 genotype-based tailored therapy for H. pylori infection has been found to be effective. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of a PPI-based therapy.

Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics.

The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.

Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy.

BACKGROUNDS AND AIMS: Eradication rates of Helicobacter pylori by a proton pump inhibitor-based triple therapy depend on CYP2C19 genotype status. We investigated whether gastric acid inhibition during an eradication therapy would influence the eradication rates attained by the triple therapy. METHODS: Thirty-two patients with H. pylori infection underwent the first-line triple therapy with lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 400 mg b.i.d. for 1 week. In all 32 patients, the 24-hour intragastric pH monitoring was performed on day 6 during the treatment period. RESULTS: The intention-to-treat-based eradication rate by the first-line therapy was 75.0% (24/32, 95%CI: 56.60-88.54%). In patients with successful eradication, the median 24-hour pH was 6.4 (range; 5.0-7.6), which was significantly higher than that in patients without eradication [5.2 (2.2-6.2), p = .0131]. The median percentage time of pH < 4.0 during 24-hour postdose in patients with eradication [0.5% (0.0-31.6%)] was significantly shorter than that in patients without eradication [26.7% (6.0-72.2%), p = .0017]. These parameters for acid inhibition significantly differed among the different CYP2C19 genotype groups. When the percentage time of pH < 4.0 and 24-hour pH were attained < 10% and > 6.0, respectively, during the eradication treatment, the majority of patients could eradicate H. pylori infection, irrespective of the bacterial susceptibility to clarithromycin. CONCLUSIONS: The sustained intragastric pH > 4.0 for a longer postdose time appears to be required for a successful eradication of H. pylori with lansoprazole and acid-labile antibiotics.

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. METHODS: The IL-10-1082 (A/G)/-819 (T/C)/-592 (A/C) polymorphisms were assessed in Helicobacter pylori-positive patients with gastritis only (n = 162), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and H. pylori-negative controls (n = 168) by allele specific primer-polymerase chain reaction methods. RESULTS: The carriage of IL-10-592 C (age and sex-adjusted odds ratio [OR]: 1.851, 95% confidence interval [CI]: 1.018-3.380) and IL-10-819 C (adjusted OR: 1.868, 95%CI: 1.023-3.411) allele were associated with an increased risk for gastric cancer development, not gastric ulcer and duodenal ulcer. The IL-10-1082 polymorphism had no association with development of gastric cancer and peptic ulcers. The presence of the ATA/GCC haplotype of IL-10-1082/-819/-592 polymorphism significantly increased the risk of gastric cancer development (adjusted OR: 2.805, 95%CI: 1.258-6.254) compared with presence of the ATA/ATA haplotype. CONCLUSIONS: The IL-10-1082/-819/-592 genotype status and haplotype were associated with an increased risk for gastric cancer development, not peptic ulcer, in Japan. The genotyping test of this anti-inflammatory cytokine would be useful for the detection of individuals with higher risk of gastric cancer development.

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 2,142 and 2,143 of the 23S rRNA gene of H. pylori. METHODS: In total, 112 patients with H. pylori infection based on positive results of a rapid urease test (RUT) were enrolled in the study. Thirty-five had failed to eradicate H. pylori by a clarithromycin-based regimen. DNA was extracted from the RUT-positive gastric tissue samples. SNPs from adenine to guanine at positions 2,142 and 2,143 of the 23S rRNA of H. pylori (A2,142G and A2,143G) were determined by the ASP-PCR method. Minimum inhibitory concentrations (MICs) of clarithromycin for H. pylori were also measured. RESULTS: Forty-nine of 112 patients were infected with wild-type strains of H. pylori. Thirty-nine patients were infected with strains with A2,143G mutations. Twenty-three patients were infected with both wild-type strains and those with A2,143G mutations. Only one patient was infected with the strain with A2,142G mutation. H. pylori strains with A2,143G or A2,142G mutation had significantly higher MICs for clarithromycin. CONCLUSION: The ASP-PCR assay for 23S rRNA mutation of H. pylori is a useful method to detect clarithromycin-resistant strains of H. pylori easily.