Comparative immunoproteomics of identification and characterization of virulence factors from Helicobacter pylori related to gastric cancer

Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.     

Helicobacter pylori seropositivity and risk of lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.     

Helicobacter pylori Multiplex Serology

Background:  Helicobacter pylori infection is associated with severe gastrointestinal disease including cancer. It induces complex antibody responses that might vary depending on disease state but currently cannot be assessed adequately. The objective of this work was the development of a sensitive and specific H. pylori multiplex serology assay with high-throughput capability that allows simultaneous detection of antibodies to a protein array.
Methods:  Seventeen proteins of up to three H. pylori strains (26695, G27, 151), including CagA, VacA, UreA, Catalase, Omp, and GroEL, were recombinantly expressed as glutathione- S -transferase fusion proteins, affinity-purified, and used as antigens in a fluorescent bead-based antibody-binding assay. Reference sera (n   =   317) characterized by commercial assays (screening ELISA with Western blot confirmation) were used for validation.
Results:  H. pylori seropositivity by multiplex serology defined as reactivity with at least four proteins showed good agreement (kappa: 0.70) with commercial serologic assay classification, and a sensitivity of 89% and specificity of 82%. For individual antigens, agreement with Western blot was good for CagA (kappa: 0.77), moderate for UreA (kappa: 0.53), and weak for VacA (kappa: 0.12). Of the 13 proteins expressed from two strains, only VacA showed serologic strain differences. High antibody reactivity to CagA (Type I infection) was negatively associated with antibodies to GroEL, Cad, CagM, catalase, HcpC, NapA, and UreA, suggesting type-specific differences in protein expression patterns and/or immune response.
Conclusion:  With its high-throughput and simultaneous detection abilities, H. pylori multiplex serology appears suited as tool for large seroepidemiologic studies assessing H. pylori prevalence, antibody patterns, and associations with specific diseases.     

CagA and VacA: Virulence Factors of Helicobacter pylori in Thai patients with Gastroduodenal Diseases

Background. The aim of this study was to assess the seroprevalence of cytotoxin-associated gene A ( cag A) and vacuolating cytotoxin gene A ( vac A) of Helicobacter pylori in selected Thai populations with specific gastroduodenal diseases.
Materials and Methods. The immunoblot assay was used to detect serum antibodies against CagA and VacA obtained from the following patients: 87 cases of nonulcer dyspepsia (NUD), 61 cases of duodenal ulcer (DU), 49 cases of gastric ulcer (GU), and 10 cases of gastric cancer (GC).
Results. Serum antibodies to CagA were detected in 75.4% of all patients (70.1% of NUD, 78.7% of DU, 77.6% of GU, and 90% of GC). Although the prevalence of CagA seropositivity in GC patients was higher than in the other three groups, the difference was not statistically significant ( p > .05).
Conclusions. The high seroprevalence of the CagA-positive H. pylori strain in patients with peptic ulcer, GC, and NUD indicates that this strain is common in Thai patients with gastroduodenal diseases. Furthermore, phenotypic classification of H. pylori into type 1 (CagA-positive, VacA-positive) and type 2 (CagA-negative, VacA-negative) is not a useful marker for screening patients with severe forms of gastroduodenal diseases.     

Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia

BACKGROUND: Distinct virulence factors of Helicobacter pylori have been associated with clinical outcome of the infection; however, considerable variations have been reported from different geographic regions and data on genotypes of Turkish H. pylori isolates are sparse. AIM: To determine the prevalence of specific genotypes of H. pylori in Turkish patients with dyspepsia. MATERIALS AND METHODS: Ninety-three H. pylori-positive patients [30 with non-ulcer dyspepsia (NUD), 30 with duodenal ulcer (DU), and 33 with gastric cancer (GC)] who were admitted to our endoscopy unit due to dyspepsia were enrolled in the study. H. pylori infection was confirmed in all patients by histology and rapid urease test (RUT). The presence of vacA alleles, cagA, cagE, iceA, and babA2 genotypes were determined by polymerase chain reaction (PCR). Chi-squared test and Fisher's exact test were used for statistical comparisons and multivariate regression analysis was performed to find out independent predictors of different clinical outcomes. RESULTS: Turkish strains examined predominantly possessed the vacA s1,m2 (48.4%) and s1,m1 (40.7%) genotypes. The vacA s1a genotype was detected in 66.7, 96.4, and 87.9% of isolates from patients with NUD, DU, and GC, respectively, and its presence was significantly associated with that of DU (p = .004), GC (p = .043), and cagA gene (p = .021). None of the cases was found to harbor the s1c genotype. The frequencies of the cagA and cagE genes among studied isolates were 73.6 and 59.3%, respectively. The cagA gene was significantly associated with the presence of DU (p = .004) and GC (p = .003), and the cagE gene, too, was significantly associated with the presence of DU (p = .002) and GC (p = .000). All H. pylori isolates possessed the iceA gene. In all, 68 isolates (74.7%) were positive for iceA1 and 23 (25.3%) for iceA2. The frequency of icea1 gene was significantly higher in cases with GC (85%) than in cases with NUD (60%) (p = .026). The frequency of babA2 gene was 23.3, 46.4, and 87.9% in isolates of patients with NUD, DU, and GC, respectively. When compared to cases with NUD (p = .000) and DU (p = .000), the presence of babA2 gene was significantly higher in cases with GC. Multivariate regression analysis disclosed cagE (p = .006) and vacA s1a (p = .027) genotypes to be independent predictors of DU and babA2 (p = .000) and cagE (p = .013) genotypes to be independent predictors of GC. CONCLUSIONS: H. pylori vacA s1a, cagA, cagE genotypes have significant relations with the presence of DU and GC, and iceA1, babA2 with GC in Turkish patients with dyspepsia, whereas cagE and vacA s1a genotypes are independent predictors of DU, and babA2 and cagE genotypes are independent predictors of GC.     

CagA-positive Helicobacter pylori infection may increase the risk of food allergy development.

The aim of this study was to test whether patients with symptomatic food allergy and significant levels of immunoglobulin E (IgE) to alimentary antigens were more likely infected by H. pylori, especially by strains expressing the CagA protein, with respect to controls. A group of 38 patients with symptomatic food allergy and 53 age-matched controls were examined serologically for H. pylori infectious status, and for CagA seropositivity. IgE to alimentary allergens were measured by a commercial kit. The prevalence of H. pylori infection in patients with food allergy and controls was similar (42.1%, and 48.3%, respectively). However, anti-CagA antibodies in H. pylori-infected persons were detected in 62.5% of patients with food allergy, and 28% of controls (P = 0.030, odds ratio = 4.29). The mean level of IgE to the most common alimentary antigens in serum samples from infected patients with anti-CagA antibodies was significantly higher than in CagA-negative infected patients: 3.28 kU/L (SD 3.93), vs. 1.99 kU/L (SD 1.53), P = 0.002, 95% confidence interval = 0.61 to 2.53). Infection by CagA-positive H. pylori increases the risk of developing food allergy.     

Aneurysm and Helicobacter pylori relationship: the seropositivity of CagA, VacA and other antigens of Helicobacter pylori in abdominal and ascending aortic aneurysms

Helicobacter pylori is thought to be related to atherosclerosis and aneurysm development. We aimed to detect virulance factors of H. pylori and examine the potential etiopathogenetic relationship between aortic aneurysm and H. pylori, 58 abdominal aortic aneurysm (AAA) and 38 ascending aortic aneurysm (AsAA) cases and 57 Healty control group (HCG) were included. We investigated H. pylori IgG by ELISA and virulance factors by Western-Blot (WB) method. No difference was found between AAA (67.24%), AsAA (73.68%) and HCG (57.89%) for H. pylori IgG (p > 0.05). A significant difference was found between AsAA (78.95%) and HCG (57.89%) for H.pylori IgG (p < 0.05) by ELISA and a significant difference was found only between AsAA (100%) and HCG (37.5%) for H. pylori IgG in the 45-55 age group by WB. A statistically significant difference was found between AAA and AsAA for VacA and CagA + VacA and CagA + VacA + UreA antigens and also a significant difference was found between AsAA and HCG for CagA + UreA antigens (p < 0.05). Finally, we suggest that H. pylori VacA has a more important role than CagA in the development of two aneurysms especially in ruptured AAA. New extended studies detecting H. pylori DNA are needed to detect the aetiopathogenesis between aneurysm types and H. pylori.     

LTA 252GG and GA Genotypes are Associated with Diffuse-Type Noncardia Gastric Cancer Risk in the Japanese Population

Background:  There are limited numbers of reports on the association of lymphotoxin-alpha ( LTA ) genotypes with gastric cancer.
Methods:  A nested case–control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose.
Results:  LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3–6.3), p  =   .01, and RR = 2.7 (95% CI: 1.5–4.8), p  <   .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2–0.7), p  <   .001) and never smoking (RR = 0.4 (95% CI: 0.3–0.6), p  <   .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G -allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7–5.9), p  =   .009).
Conclusion:  The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.     

Risk factors associated with gastric cancer in patients with a duodenal ulcer

Background: Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. Materials and Methods: A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. Results: Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus‐predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients with a DU, moderate–severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46–9.36, and OR, 7.72; 95% CI, 3.18–18.7, respectively). Additionally, moderate–severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06–18.5, and OR, 9.25, 95% CI, 2.39–35.8, respectively). Conclusions: A DU is not rare in patients with GC in a high‐risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development.     

The prevalence and incidence of Helicobacter pylori infections among young recruits during service in the Hungarian Army

BACKGROUND: A vast number of data indicate that the prevalence of Helicobacter pylori infections is positively correlated with age and is different in various countries. Although our knowledge of transmission of H. pylori is very limited, it is reasonable to assume that it could be much more contagious in closed communities, for example in garrisons, than in normal populations. METHODS: Young male recruits (aged 19-23 years) in the Hungarian Army were tested for seropositivity at the beginning and at the end of their military service. RESULTS: The prevalence of H. pylori seropositivity was found to be 23% (*CI95%: 21-24%) among the young male recruits. Seroconversion among the formerly seronegative persons after completing either their 9-month or 6-month military service was 30% (CI95%: 25-35%) and 23% (CI95%: 8-45%), respectively. In those groups, where either the H. pylori infection was eradicated by antibiotics or hygienic countermeasures were introduced, the infection rate was reduced from 23% to 11% (CI95%: 3-25%) and to 0% (CI95%: 0-6%); p > .2 and p < .002, respectively. CONCLUSION: Our data suggest that, although H. pylori has a very high contagiosity in closed communities, its spread can be reduced or even prevented by medication of the infected persons and/or by improving the hygienic conditions and introducing anti-infective sanitary regulations.     

Helicobacter pylori infection in children in Estonia: decreasing seroprevalence during the 11-year period of profound socioeconomic changes

BACKGROUND: The prevalence of Helicobacter pylori infection is inversely associated with socioeconomic conditions in childhood. In Estonia, a high prevalence of H. pylori infection has been observed among children born in 1987 and earlier. Since 1991, after the dissolution of the USSR, profound social and economic changes have taken place in the country. The aim of the study was to evaluate changes in the seroprevalence of H. pylori infection among children in the period 1991-2002. MATERIALS AND METHODS: The hospital-based study population consisted of two groups of children enrolled in 1991 (n = 425) and 2002 (n = 296) according to the same inclusion criteria. The immunoglobulin G antibodies to the cell surface proteins of H. pylori were determined by enzyme-linked immunosorbent assay, and the sera with the borderline results were analyzed by immunoblot analysis. Multiple regression analysis was used to determine the associations between H. pylori seropositivity and different variables such as demographic characteristics, diagnoses and year of enrollment. RESULTS: The only two variables linked independently to H. pylori serostatus were age and year of enrollment: the adjusted odds of being H. pylori seropositive were 1.92 [95% confidence interval (CI) 1.33-2.76] times higher for the children enrolled in 1991 compared with the children enrolled in 2002. The age-standardized seroprevalence rate was 42.2% (95% CI 37.4-47.0%) for the group of 1991 and 28.1% (95% CI 23.1-33.6%) for the group of 2002. CONCLUSION: The prevalence of H. pylori infection among children has significantly decreased during the 11-year period of profound socioeconomic changes in Estonia.     

A Population-Based Epidemiologic Study of Helicobacter Pylori Infection and its Association with Systemic Inflammation

Background:  Infection with Helicobacter pylori is associated with a variety of non-gastrointestinal sequelae. These may be mediated by an increase in systemic inflammation. We assessed if serologic evidence of infection with H. pylori is associated with increased serum C-reactive protein (CRP) levels.
Methods:  The study design consisted of a randomly selected, cross-sectional population-based study of 2633 individuals phenotyped in 1991, of whom 2361 participants provided serum samples to permit measurement of H. pylori 's serologic status and CRP levels.
Results:  Male gender (odds ratio (OR): 1.65; 95% confidence interval (CI): 1.23–2.21), age (OR per year: 1.05; 95% CI: 1.04–1.06), height (OR per meter: 0.05; 95% CI: 0.01–0.24), current smoking habit (compared with never smokers, OR: 1.46; 95% CI: 1.13–1.88), and less affluent socioeconomic status were associated with increased odds of being seropositive for H. pylori . Helicobacter pylori infection was associated with increased risk of having an elevated serum CRP (above 3 mg/L) after adjustment for gender, age, height, smoking status, and socioeconomic status (OR: 1.32; 95% CI: 1.05–1.67). Similar associations were seen using a threshold for elevated serum CRP of greater than 1 mg/L.
Conclusions:  Our data suggest that infection with H. pylori is associated with increased systemic inflammation. This suggests one potential mechanism to explain the extra-gastrointestinal conditions associated with H. pylori infection.     

Helicobacter pylori antibodies and gastric cancer: a gender-related difference

Helicobacter pylori has been proposed as a causative agent of gastric cancer. The aim of this study was to define serum antibodies response against different H. pylori antigens in patients with gastric cancer. Serum samples were collected from 115 Lithuanian patients with non-cardia gastric cancer and 110 age- and sex-matched controls without cancer. Heat-stable, low-molecular-mass, and outer membrane proteins were used as antigens to analyze serum IgG antibody response against H. pylori by enzyme-linked immunosorbent assay. Seroprevalence of H. pylori using low-molecular-mass antigen was significantly higher in gastric cancer patients, compared to controls (77% versus 57%, p<0.05). Significant differences in the prevalence of H. pylori infection between gastric cancer patients and controls were found in females using all three studied antigens: heat-stable (98% versus 84%, p<0.05), low-molecular-mass (88% versus 48%, p<0.05) and outer membrane proteins (78% versus 57%, p<0.05). In males, no significant differences were revealed between gastric cancer patients and controls. There may be other cofactors in addition to H. pylori that are important for the development of gastric cancer. H. pylori seems, however, to be a more important for development of gastric cancer in females than in males or males may have more confounding risk factors for gastric cancer than females.     

Genetic susceptibility and risk of gastric cancer in a human population of Cauca, Colombia

Gastric cancer (GC) is the main cause of mortality by cancer in Colombia. Glutathione S-transferase (GST) enzymes are involved in the detoxification of many environmental carcinogens. The homozygous deletions of glutathione S-transferase M1 (GSTM1-0) and glutathione S-transferase T1 (GSTT1-0) have been associated with several types of cancer. The risk to develop GC has been associated with environmental factors and Helicobacter pylori infection. The tumor necrosis factor (TNF-alpha) and its levels are increased in patients infected with H. pylori. A G/ A transition in the position -308 of the promoter of the TNF-alpha has been related in several studies to an increased expression of the gene and is associated with susceptibility to GC. The association of these polymorphisms with GC and the interaction with other risk factors (life style) were investigated. Blood samples were obtained from 46 GC patients and 96 controls. The logistic regression model was used to obtain the odds ratio (OR) and their 95% confidence intervals. These statistics established the association between the enzymatic polymorphisms and GC and between other independent factors and GC. The frequency of the TNF-alpha polymorphism in people infected with H. pylori was 18% in the GC population and 7% in the control group. This transition was not significantly associated with H. pylori infection and GC. The frequencies of the deletion polymorphisms for patients and controls were as follows: GSTM1 65.2% and 37.5%; GSTT1 17.4% and 14.6%. These results suggested that the GSTM1 deletion polymorphism was associated with an increased risk of gastric cancer (OR of 5.5; 95%CI, 1.7-17.2). Furthermore, other risk factors such as H. pylori infection (OR 5.58, CI 1.8-17.2), smoking (OR 6.70, CI 2.2-20.3) and alcohol intake (OR 3.27, CI 1.1-9.4) were associated with GC.     

Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy

Background. New triple therapy for eradication of Helicobacter pylori based on a proton pump inhibitor (PPI) provides a cure rate of approximately 90% with few adverse effects. Recently, a PPI-based quadruple therapy, which consists of a PPI plus bismuth-based triple therapy for 7 days, has been studied, and a sufficient eradication rate has been achieved. However, a shorter duration results in improved compliance. In this study, newly developed short-term, simple twice-daily quadruple therapy consisting of rabeprazole, amoxicillin, clarithromycin, and metronidazole (RACM) was compared with a PPI-based triple-therapy regimen for eradication of H. pylori.
Patients and Methods. This study was designed as a randomized open, prospective single-center study. Of a total of 105 H. pylori –positive patients, 55 received the RACM regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; clarithromycin, 200 mg bid; and metronidazole, 250 mg bid), and 50 received the RAC regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; and clarithromycin, 200 mg bid). Cure of the infection was assessed by HpSA ( H. pylori stool antigen immunoassay) 1 month after completion of therapy.
Results. The rates of eradication of H. pylori by RACM versus RAC were 94.5% (95% CI, 85–99) versus 80.0% (95% CI, 66–90) by intention-to-treat analysis; 98.1% (95% CI, 90–100) versus 87.0% (95% CI, 74–95) by all-patients-treated analysis; and 98.1% (95% CI, 90–100) versus 86.7% (95% CI, 73–95) by per-protocol analysis. No major adverse effects were reported, and 98.0% of patients reported complete compliance.
Conclusions. The simple twice-daily and short-term quadruple regimen for only 5 days provided an excellent eradication rate. Compliance with the regimen was high, and serious adverse effects were few. Therefore, the RACM regimen can be considered as safe and effective.     

No association between IL-1β -511 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 4667 subjects

Epidemiological studies have evaluated the association between IL-1β -511 C/T polymorphism and duodenal ulcer (DU) risk. However, the results remain conflicting. The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -511 C/T polymorphism and DU. Systematic searches of electronic databases Embase, PubMed and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 14 studies including 1887 cases and 2780 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -511 C/T polymorphism and DU (for T allele vs. C allele: OR=0.93, 95% CI=0.82-1.06; for T/T vs. C/C: OR=0.83, 95% CI=0.64-1.08; for dominant model: OR=0.93, 95% CI=0.80-1.07; and for recessive model: OR=0.87, 95% CI=0.69-1.11). Significant association was found in all genetic models for the PB subgroup and sensitivity analyses. In conclusion, our meta-analysis suggests that there was no evidence of a significant association between IL-1β -511 C/T polymorphism and DU with or without Helicobacter pylori infection, whereas a significant association was found by sensitivity analyses which showed a protective effect of the T allele against DU risk.     

Clinical relevance of the cagA,vacA and iceA genotypes of Helicobacter pylori in Brazilian clinical isolates

Infection with Helicobacter pylori strains harboring determinants of pathogenicity may lead to a strong inflammatory response in gastric mucosa. In this work, we examined the frequency of the cagA, vacA and iceA genotypes in H. pylori strains isolated from Brazilian patients and correlated these with the clinical manifestations. H. pylori was isolated from 165 patients [30 with non-ulcer dyspepsia cases (NUD); 93 peptic ulcer disease (PUD): 31 gastric ulcers (GU) and 62 duodenal ulcer disease (DU); 18 with erosive gastritis (EG); and 24 gastroesophageal reflux disease (GERD)]. Allelic variants of cagA, vacA and iceA were identified using the polymerase chain reaction. More than one H. pylori strain was detected in 28 cases (17%), and these were excluded from the statistical analysis. We were unable to confirm an association between iceA status and clinical outcome. There was a strong association between the genotype cagA-positive vacA s1 and PUD. However, logistic regression analysis showed that vacA s1 was the only predictive factor for PUD (OR=4.19; 95% CI 1.95-8.98). The presence of the less virulent strain vacA s2 was related to GERD (OR=8.59; 95% CI 2.85-25.91). Our results support the hypothesis that virulent strains may protect against the development of GERD.     

A prospective study for the association of Helicobacter pylori infection to a multidimensional measure for recurrent abdominal pain in children

BACKGROUND: There is a controversial association between Helicobacter pylori infection and recurrent abdominal pain (RAP) in childhood and inconsistent information on specific symptomatology of the infection. AIMS: To examine the prevalence of H. pylori infection among children with RAP compared to asymptomatic children. METHODS: Two prospective studies were conducted. The first study enrolled 223 children diagnosed with RAP from two pediatric gastroenterology clinics in Houston, Texas. Children were qualified if they were identified by their physician as having RAP. A new multidimensional measure for RAP (MM-RAP) consisting of four scales (pain intensity scale, symptoms scale, disability scale, and satisfaction scale) was administered to each child/parent. The second study enrolled 330 asymptomatic children from the same community who did not have any upper gastrointestinal symptoms. Symptomatic and asymptomatic children underwent (13)C-urea breath testing. RESULTS: In the first study, the prevalence of H. pylori in children with RAP was 11% and fell with age from 20% at age < or = 5 years to 7% for children > 10 years (OR = 2.7, 95% CI = 0.7-11.2). There was no association between the mother's educational level and H. pylori prevalence; (12% among children whose mothers completed college versus 11% among those who had elementary school, p = .8). No relationship was found between H. pylori and mean scores of the RAP scales. In the second study, the prevalence of H. pylori in asymptomatic children was 17% and increased with age from 11% for children < or = 5 years to 40% for children > 10 years (OR = 5.4, 95% CI = 2.0-13.8). The mother's educational level was inversely correlated with H. pylori (OR = 3.0, 95% CI = 2.2-6.1, p < .01). CONCLUSIONS: The epidemiologic patterns of H. pylori infection differed significantly between symptomatic and asymptomatic children. Younger children suffering from RAP are more likely to be infected with H. pylori than older children with the same complaint, suggesting that early acquisition may manifest in symptoms that lead to clinic visits.     

Prevalence of duodenal ulcer-promoting gene (dupA) of Helicobacter pylori in patients with duodenal ulcer in North Indian population

BACKGROUND: The duodenal ulcer (DU)-promoting gene (dupA) of Helicobacter pylori has been identified as a novel virulent marker associated with an increased risk for DU. The presence or absence of dupA gene of H. pylori present in patients with DU and functional dyspepsia in North Indian population was studied by polymerase chain reaction (PCR) and hybridization analysis. MATERIALS AND METHODS: One hundred and sixty-six patients (96 DU and 70 functional dyspepsia) were included in this study. In addition, sequence diversity of dupA gene of H. pylori found in these patients was analyzed by sequencing the PCR products jhp0917 and jhp0918 on both strands with appropriate primers. RESULTS: PCR and hybridization analyses indicated that dupA gene was present in 37.5% (36/96) of H. pylori strains isolated from DU patients and 22.86% (16/70) of functional dyspepsia patients (p < or = .05). Of these, 35 patients with DU (97.2%) and 14 patients with functional dyspepsia (81.25%) were infected by H. pylori positive for cagA genotype. Furthermore, the presence of dupA was significantly associated with the cagA-positive genotype (p < or = .02). CONCLUSION: Results of our study have shown that significant association of dupA gene with DU in this population. The dupA gene can be considered as a novel virulent marker for DU in this population.     

Comparison of Meal-Stimulated Serum Gastrin Response in Helicobacter pylori–Positive Duodenal Ulcer and Asymptomatic Volunteers With and Without H. pylori Infection

Background. Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori ( H. pylori ) infection plays an important role in the pathogenesis of DU.
Materials and Methods. Subjects consisted of 15 patients with H. pylori –positive DU, 10 H. pylori –positive volunteers, and 35 H. pylori –negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1-hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay.
Results. Meal-stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori –positive and –negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper-IGR and normo-IGR. Serum PG I concentration was significantly higher in the hyper-IGR than in the normo-IGR group.
Conclusions. The DU patients differed in some way (other than H. pylori infection) from the H. pylori –positive healthy volunteers. The fact that hyper-IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors.