Colonisation density and topographic localisation of Helicobacter pylori do not depend on the cagA status

AIMS: To explore the correlation between the cagA status of Helicobacter pylori and the density and topographic localisation of H pylori. METHODS: Gastric antral biopsy specimens were taken from 716 consecutive patients, including 293 H pylori positive patients (124 men, 169 women; mean age, 52.6 years; range, 12-87). A serum sample was taken for determination of IgG anti-CagA antibodies (sensitivity of 94.4% and specificity of 92.5%). The density of H pylori was assessed semiquantitatively (grades I-IV) in biopsy specimens stained with the modified Giemsa stain. Topographic localisation was classified as follows: score A, H pylori closely attached to the mucosa; score B, H pylori attached to the mucosa and in the mucus; and score C, H pylori solely in the mucus. RESULTS: CagA antibodies were present in 154 (52.5%) of the patients. There was no significant difference in colonisation density and cagA status: grade I, 23 (14%); grade II, 78 (50.6%); grade III, 42 (27.5%); and grade IV, 11 (7.2%) in the cagA(+) strains and 29 (21.2%), 57 (40.8%), 38 (27%), and 15 (11%), respectively, in the cagA(-) strains. There was no difference in topographic localisation between cagA(+) and cagA(-)H pylori. Mean anti-CagA titres were 0.84, 0.84, 0.89, and 0.73 in patients with grades I-IV bacterial density, respectively. CONCLUSION: Antibody titres do not correlate with H pylori density and there is no difference in density between cagA(+) and cagA(-)H pylori strains. In addition there is no difference in topographic localisation between cagA(+) and cagA(-) H pylori strains.     

Helicobacter pylori cagA and vacA cytotoxin genes in Changsha,China

Cytotoxin-associated protein (cagA) and the vacuolating cytotoxin (vacA) encoded by cagA and vacA genes are virulence determinants of Helicobacter pylori. In earlier studies among Chinese patients, all H. pylori strains were cagA-positive and vacAs1a/m2 type. Here, we determine the cagA, vacA and allele status of H. pylori strains isolated from patients with upper gastrointestinal symptoms in Changsha, China. Forty strains of H. pylori isolated from patients with peptic ulcer disease between March 1997 and August 1999 were recovered from storage at -80 degrees C and studied by the polymerase chain reaction (PCR) for cagA and vacA genotypes. cagA was positive in 75% of H. pylori isolates. Patients with peptic ulcer demonstrated cagA in 83% (15/18), compared with 68% (15/22) patients with superficial gastritis. vacAs1 allele was carried in 82.5% (33/40) isolates, of which 52.5% (21/40) were subtype vacAs1a/m2 and 17.5% (7/40) were subtype vacAs1b/m2.     

Correlation between IL-8 induction, cagA status and vacA genotypes in 153 French Helicobacter pylori isolates

The polymorphism of clinical presentations associated with Helicobacter pylori infection is potentially due to differences in the virulence of individual strains. H. pylori virulence has been associated with the ability to induce secretion of interleukin-8 (IL-8), the vacA genotypes, and the cagA status. The aim of this study was to determine the virulence profiles of 153 French H. pylori isolates on the basis of vacA genotypes, cagA status, and IL-8 induction ability. A total of 153 H. pylori isolates from patients with chronic gastritis (n = 74) or gastro-duodenal ulcers (n = 79) was examined for vacA genotypes and cagA status by polymerase chain reaction (PCR) and dot blot, and for their ability to induce IL-8 secretion by HEp-2 cells. The prevalence of vacA genotypes was: s1/m1 44.3%, s1/m2 24.9%, and s2/m2 23.5%. The cagA gene was present in 64% of the strains. IL-8 secretion was induced by 58.7% of the isolates. The presence of the cagA gene was significantly correlated with the s1/m1 vacA genotype and with the induction of IL-8. Thirty-four strains were atypical (cagA-positive/IL-8 noninducer or cagA-negative/IL-8 inducer). vacA genotypes, cagA status, and IL-8 induction ability are not correlated with the presence or absence of ulcer. The cagA status is not sufficient to predict the proinflammatory ability of H. pylori.     

Serologic detection of infection with cagA+ Helicobacter pylori strains.

Approximately 60% of Helicobacter pylori isolates possess the cagA gene and express its 120- to 140-kDa product (CagA). In this study, the cagA gene was detected in H. pylori isolates from 26 (81.3%) of 32 patients with duodenal ulcers (DU), 17 (68.0%) of 25 patients with gastric ulcers, and 23 (59.0%) of 39 patients with nonulcer dyspepsia (NUD). By Western blotting (immunoblotting) with antiserum to CagA, in vitro CagA expression was demonstrated for 95.5% of cagA+ strains compared with 0% of strains lacking cagA. Sera from patients infected with cagA+ strains (n = 66) reacted with recombinant CagA in an enzyme-linked immunosorbent assay to a significantly greater extent than either sera from patients infected with strains lacking cagA (n = 30) or sera from uninfected persons (n = 25) (P < 0.001). A strain lacking cagA was isolated from eight patients who had serum immunoglobulin G antibodies to CagA, which suggests that these patients were infected with multiple strains. Serum immunoglobulin G antibodies to CagA were present in 87.5, 76.0, and 56.4% of patients with DU, gastric ulcers, and NUD, respectively (odds ratio, 5.41; 95% confidence interval, 1.44 to 24.72; P = 0.004 [DU versus NUD]). These data demonstrate an association between infection with cagA+ H. pylori and the presence of duodenal ulceration and indicate that serologic testing is a sensitive method for detecting infection with cagA+ strains.     

Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the cagA gene

Helicobacter pylori CagA is translocated into gastric epithelial cells by a type IV secretion system and interacts with the Src homology 2 phosphatase, altering cell morphology. Multiple EPIYA motifs in CagA are associated with increased activity in cells and with gastric cancer. The aim of this work was to study the heterogeneity in activity in cells of multiple H. pylori single colonies isolated from a single patient and its association with polymorphism in cagA. The presence of cagA, cagE, cagT, and cag10 was studied with 318 H. pylori isolates from the antra and corpora of 18 patients. AGS gastric epithelial cells were infected with 75 isolates, and interleukin-8 (IL-8) secretion, cytoskeletal changes, CagA translocation, and tyrosine phosphorylation were measured. The cagA 3'-variable region was sequenced for 30 isolates to determine the number and types of EPIYA motifs. Isolates from an individual stomach were usually genetically related and had quantitatively similar phenotypic effects on cells (IL-8 induction and cytoskeletal changes). However, strains from different patients with similar CagA EPIYA motif patterns varied widely in these phenotypes. Among isolates with an EPIYA-ABC pattern, the phenotype was variable: IL-8 induction ranged from 200 to 1,200 pg/ml, and morphological changes occurred in 20 to 70% of cells. In several cases, cagA sequence diversity appeared to explain the lack of CagA activity, as isolates with an EPIYA-ACC pattern or a modified B motif had reduced cell activity. cag pathogenicity island-positive H. pylori isolates displayed a high level of heterogeneity in the capacity to induce IL-8 secretion and morphological changes; an absent or modified B motif was associated with low activity.     

Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori.

Helicobacter pylori now is recognized as an etiological agent in chronic superficial gastritis and peptic ulcer disease. Although only about 60% of H. pylori isolates produce an immunodominant 128-kDa antigen (CagA; cytotoxin-associated gene product), virtually all H. pylori-infected patients with duodenal ulceration develop a serologic response to the 128-kDa protein, which suggests an association of this gene with ulceration. The cloned cagA gene from H. pylori 84-183 was disrupted by insertion of a kanamycin resistance gene, and this inactivated cagA construct was introduced into H. pylori 84-183 by electrotransformation. Southern hybridization of kanamycin-resistant H. pylori transformants demonstrated that the wild-type cagA gene had been disrupted by insertion of the kanamycin cassette, and immunoblot analysis showed that the mutant strains no longer produced the 128-kDa CagA protein. Similar results were obtained when the cagA mutation was introduced by natural transformation into H. pylori 60190, a high-level toxin-producing strain. The cagA-negative H. pylori strains showed cytotoxin, urease, and phospholipase C activities, C3 binding and adherence similar to those of the isogenic wild-type strains. These findings demonstrate that the cagA gene product does not affect the vacuolating cytotoxin activity of H. pylori.     

Co-expression in Helicobacter pylori of cagA and non-opsonic neutrophil activation enhances the association with peptic ulcer disease

AIMS: To investigate the association of cagA positivity and non-opsonic neutrophil activation capacity in wild-type Helicobacter pylori strains with peptic ulcer disease or chronic gastritis only. METHODS: Helicobacter pylori were isolated from antral biopsies of 53 consecutive patients with chronic antral gastritis, of whom 24 had peptic ulcer disease endoscopically. The presence of cagA, a marker for the cag pathogenicity island, was determined by polymerase chain reaction with specific oligonucleotide primers, and non-opsonic neutrophil activation capacity by luminol enhanced chemiluminescence. RESULTS: The cagA gene was present in 39 of 53 (73.6%) strains, 20 of which (83.3%) were from the 24 patients with peptic ulcer disease and 19 (65.5%) from the 29 patients with chronic gastritis only. Non-opsonic neutrophil activation was found in 29 (54.7%) strains, 16 of which (66.7%) were from patients with peptic ulcer disease, and 13 (44.8%) from those with chronic gastritis. Non-opsonic neutrophil activation was found more frequently in cagA+ than cagA- strains (59% v 42.9%). Whereas four of the 14 cagA- strains and eight of the 24 non-opsonic neutrophil activation negative strains were from patients with peptic ulcer disease, only two of 24 (8.3%) peptic ulcer disease strains expressed neither cagA nor non-opsonic neutrophil activation. The cagA gene and non-opsonic neutrophil activation capacity were co-expressed in 14 of 24 (58.3%) strains from patients with peptic ulcer disease, and in nine of 29 (31%) strains from individuals with chronic gastritis. CONCLUSIONS: Positivity for cagA and non-opsonic neutrophil activation occur independently in wild-type H pylori strains. However, co-expression of the two markers enhanced the prediction of peptic ulcer disease.     

Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens

The Helicobacter pylori chromosomal cluster of genes known as the cytotoxin-associated gene (cag) island may have different compositions in infecting strains. In this study, we analyzed 150 single colonies obtained from gastric biopsy specimens from 10 patients infected with cagA-positive H. pylori strains and sweep isolates (isolates harvested with sweep in different points of the plate) from 6 patients infected with cagA-negative strains. Three loci in the cag island (cagA, cagE, and virB11) and the conserved gene glmM (ureC) were investigated by PCR. The levels of anti-H. pylori and anti-CagA antibodies in patient sera were also measured. For subjects infected with cagA-negative strains, all sweep isolates were also negative for cagE and virB11, suggesting the complete absence of the cag island. For subjects infected with cagA-positive strains, most of the isolates were positive for all three genes studied, whereas 24.7% of the isolates had a partial or total deletion of the cag island. cagA, cagE, and virB11 were, respectively, present in 87.3, 77.3, and 90% of the colonies. The deletion of virB11 was always associated with the deletion of cagA and/or cagE. H. pylori colonies with different cag genotypes were isolated within a single gastric biopsy specimen from 3 of the 10 patients and were further characterized by random amplified polymorphic DNA (RAPD) analysis and by sequencing of an arbitrarily selected gene segment. Although the colonies had different cag genotypes, their RAPD profiles were highly similar within each patient, and the nucleotide sequences of the selected gene segment were identical. All of the patients had detectable antibodies against H. pylori, and 9 of 10 had anti-CagA antibodies. In conclusion, we show that a single infecting H. pylori strain may include variable proportions of colony subtypes with different cag genotypes. The extension of our analysis to patients with well-characterized gastric diseases may provide significant information on the relationship between cag genotypes and clinical outcomes of H. pylori infections.     

Genotypic, clinical, and demographic characteristics of children infected with Helicobacter pylori

Helicobacter pylori isolates vary between geographic regions. Certain H. pylori genotypes may be associated with disease outcome. Thirty-eight children underwent diagnostic upper endoscopy at four medical centers and were retrospectively analyzed to determine if H. pylori virulence genes were associated with endoscopic disease severity, histologic parameters, and host demographics. The H. pylori virulence genotype was analyzed by a reverse hybridization line probe assay and type-specific PCR. Endoscopic ulcers or erosions were found in 17 (45%) patients, with 13 (34%) of these patients having antral nodularity. Histological gastritis, of varying severity, was present in all children. Four patients harbored more than one H. pylori strain: one subject had both cagA(+) and cagA-negative strains, while three patients harbored either two different cagA-negative strains (two children) or two cagA(+) strains (one child). There were 28 (74%) cagA(+) isolates; 19 were associated with the vacA s1b genotype, 7 were associated with the vacA s1a genotype, 1 was associated with the vacA s1c genotype, and 1 was associated with the s2 genotype. Of 14 cagA-negative isolates, 6 were vacA s2 genotype, 4 were vacA s1b, 3 were vacA s1a, and 1 was vacA s1c. Nine of ten (90%) Hispanics had similar H. pylori strains (vacA s1b,m1), and all Asian-Canadian children were infected by strains with vacA s1c genotype. No correlation between H. pylori strain and endoscopic or histopathologic abnormalities was found. This study provides a baseline framework of North American children and their H. pylori strains, serving as a powerful epidemiological tool for prospective investigations to better understand the transmission and evolution of diverse disease outcomes.     

Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens.

A PCR assay for the detection of Helicobacter pylori in gastric biopsy specimens with specific primers for ureC gene amplification (herein referred to as ureC PCR) was compared with other routine invasive methods (culture, the rapid-urease test, and Giemsa staining of histological sections) with samples from a group of 104 consecutive dyspeptic patients. Bacteria were found in 40 (38.5%), 38 (36.5%), 36 (34.6%), and 35 (33.7%) of the patients by ureC PCR, culture, the rapid-urease test, and Giemsa stain, respectively. Sixty-three patients had negative cultures, negative histological examinations, and negative rapid-urease test results, and 61 of these patients were also negative by ureC PCR. ureC PCR detected H. pylori in two culture-negative patients. In parallel, a PCR-based assay to detect the H. pylori cytotoxin-associated antigen (cagA) gene, a putative virulence gene, was also developed. To assess the likelihood of detection of H. pylori genes directly from gastric biopsy samples and from the corresponding H. pylori isolates, specimens from 31 patients were subjected to PCR with ureC- and cagA-targeting primers. All 31 biopsy specimens and the corresponding H. pylori isolates were positive in the ureC PCR. H. pylori strains that were cagA positive also gave positive cagA PCR fragments with biopsy specimens from the same patients. All ureC PCR-positive patients were examined; biopsy specimens from 10 of 11 (91.7%) duodenal ulcer patients harbored H. pylori cagA-positive strains, whereas 19 of26 (73%) of those from patients with chronic gastritis only were found to be cagA positive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Helicobacter pylori babA2, cagA,and s1 vacA genes work synergistically in causing intestinal metaplasia

AIMS: To determine any associations between the Helicobacter pylori genes babA2, oipA, cagA and the s and m alleles of vacA. In addition, to verify whether these genes work synergistically or independently in causing gastritis, peptic ulcer, and intestinal metaplasia. METHODS: One hundred and sixty seven H pylori positive patients were studied (52 antral gastritis, 41 diffuse gastritis, 41 peptic ulcer, and 33 duodenitis). Helicobacter pylori virulence genes were amplified by means of the polymerase chain reaction. RESULTS: Significant associations were found between babA2 and the other H pylori genes studied. When considered singly, all the genes were associated with disease diagnosis, inflammation, and intestinal metaplasia. Four H pylori groups were defined. Group A: cagA-, s2m2, babA2-; group B: cagA+, s1m1, babA2+; group C: cagA+, s1m2, babA2+; group D: cagA+, s1m2, babA2-. Group A infecting strains were associated with less severe endoscopic and inflammatory conditions, whereas group B strains were associated with the worst endoscopic and inflammatory findings. Intestinal metaplasia was a rare finding in group A infected patients (< 10%), whereas it was frequent in those infected with group B strains (48%). CONCLUSIONS: The H pylori genes cagA, oipA "on", s1 and m1 vacA, and babA2 are associated with each other, possibly as a result of shared selective pressure. When coexpressed by the same H pylori strain, cagA, s1 and m1 vacA, and babA2 work synergistically in worsening inflammation. Infections caused by strains coexpressing cagA, s1m1 vacA, and babA2 are those at higher risk for intestinal metaplasia.     

Distinct variants of Helicobacter pylori cagA are associated with vacA subtypes.

The diversity of the cytotoxin-associated gene (cagA) of Helicobacter pylori was analyzed in 45 isolates obtained from nine countries. We examined variation in the 5' end of the cagA open reading frame as determined by PCR and sequencing. Phylogenetic analysis revealed the existence of at least two distinct types of cagA. One variant (cagA1) was found exclusively in strains from Europe, the United States, and Australia, whereas a novel variant (cagA2) was found in strains from East Asia. The greatest diversity between cagA1 and cagA2 was found in the first 20 amino acids of the cagA open reading frame, where several consistent insertions or deletions were observed. Additional cagA sequence variants that could be classified as separate subtypes were found in two of three Peruvian and in five of seven U.S. strains tested. The calculated isoelectric point of the first 154 amino acids of the cagA1 variants (7.52 +/- 1.54) was significantly higher than that of the first 154 amino acids of the cagA2 variants (5.61 +/- 0.94; P < 0.001). Most cagA2 strains contained vacA subtype s1c (P < 0.001), and in vacA m1 strains cagA1 was more frequently observed than cagA2. These results show the epidemiological relationship between cagA and vacA at the subtype level and indicate the existence of distinct H. pylori lineages that are not uniformly distributed over the globe.     

Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan

Colonization of the stomach mucosa by Helicobacter pylori is a major cause of acute and chronic gastric pathologies in humans. Several H. pylori virulence genes that may play a role in its pathogenicity have been identified. The most important determinants are vacA and cagA in the cag pathogenicity island (cagPAI) genes. In the present study, to consider the association of molecular genetics between vacA and the cagPAI regarding clinical outcome, we selected H. pylori strains with various genotypes of vacA in Japan and sequenced full-length vacA, cagA, and cagE genes. Sequencing of vacA and cagA genes revealed variable size, whereas the cagE gene was well conserved among strains. Each of the phylogenetic trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated that all three proteins were divided into two major groups, a Western group and an East Asian group, and the distributions of isolates exhibited similar patterns among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the Western-type 3' region cagA genotype were classified into the Western group, and the strains with the s1c/m1b vacA genotype and the East Asian-type 3' cagA genotype were included in the East Asian group. In addition, the prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (chi2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of vacA and cagPAI are associated and that the Western group with vacA and cagPAI genes is associated with peptic ulcer disease.     

Relationship between Helicobacter pylori iceA, cagA, and vacA Status and Clinical Outcome: Studies in Four Different Countries

There is continuing interest in identifying Helicobacter pylori virulence factors that might predict the risk for symptomatic clinical outcomes. It has been proposed that iceA and cagA genes are such markers and can identify patients with peptic ulcers. We compared H. pylori isolates from four countries, looking at the cagA and vacA genotypes, iceA alleles, and presentation of the infection. We used PCR to examine iceA, vacA, and cagA status of 424 H. pylori isolates obtained from patients with different clinical presentations (peptic ulcer, gastric cancer, and atrophic gastritis). The H. pylori isolates examined included 107 strains from Bogota, Colombia, 70 from Houston, Tex., 135 from Seoul, Korea, and 112 from Kyoto, Japan. The predominant genotype differed among countries: the cagA-positive iceA1 vacA s1c-m1 genotype was predominant in Japan and Korea, the cagA-positive iceA2 vacA s1b-m1 genotype was predominant in the United States, and the cagA-positive iceA2 vacA s1a-m1 genotype was predominant in Colombia. There was no association between the iceA, vacA, or cagA status and clinical outcome in patients in the countries studied. iceA status shows considerable geographic differences, and neither iceA nor combinations of iceA, vacA, and cagA were helpful in predicting the clinical presentation of an H. pylori infection.     

Determination of Helicobacter pylori virulence by simple gene analysis of the cag pathogenicity island

Nucleic acid amplification was performed for five loci in the cag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagA promoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than the cagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progression.     

Characterization of Helicobacter pylori cagA and vacA genotypes among Alaskans and their correlation with clinical disease

Helicobacter pylori infection is common in Alaska. The development of severe H. pylori disease is partially determined by the virulence of the infecting strain. Here we present vacA and cagA genotype data for H. pylori strains isolated from Alaskans and their correlation with clinical disease. We enrolled patients scheduled for esophagogastroduodenoscopy and positive for H. pylori infection. Gastric biopsy specimens from the stomach antrum and fundus were cultured. We performed PCR analysis of the H. pylori vacA gene and for the presence of the cagA gene and cagA empty site. We genotyped 515 H. pylori samples from 220 Native and 66 non-Native Alaskans. We detected the cagA gene in 242/286 (85%) persons; of 222 strains that could be subtyped, 95% (212) were non-Asian cagA and 3% (6) were East Asian cagA. After removing mixed infections (n = 17), 83% of H. pylori strains had either the vacA s1m1 (120/269) or s2m2 (103/269) genotype. Sixty-six percent (68/103) of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. Infection with an H. pylori strain having the cagA gene or vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with a decreased risk of esophagitis (P = 0.003 and 0.0003, respectively). Infection with an H. pylori strain having the vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with an increased risk of peptic ulcer disease (PUD) (P = 0.003). The majority of H. pylori strains in this study carried the non-Asian cagA gene and either the vacA s1m1 or s2m2 genotype. A majority of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. There was an association of H. pylori genotype with esophagitis and PUD.     

Genetic characterisation of Helicobacter pylori isolates from an Argentinean adult population based on cag pathogenicity island right-end motifs, lspA–glmM polymorphism and iceA and vacA genotypes

Isolates of Helicobacter pylori from 88 patients were characterised by cagA status, cagA pathogenicity island (PAI) right-end motifs, iceA, vacA and lspA-glmM genotypes, primarily by PCR-based analysis, to investigate whether Argentinean isolates differed from those recovered in southern Europe or other Latin American countries. PCR-based analysis of vacA alleles was confirmed by reverse hybridisation in 56 cases, while sequence analysis was performed either when iceA and vacA genotypes could not be determined by PCR, or to investigate PCR and reverse hybridisation vacA genotyping discordance. Typing by lspA-glmM restriction fragment length polymorphism was performed with HhaI and AluI. The pattern of cag PAI right-end motifs and the prevalence of type Ia were similar to those in isolates from southern European countries, with cagA(+)/iceA1/vacA-s1 m1 being the commonest genotype. Reverse hybridisation identified a vacA-s1a/s1b recombinant allele, confirmed by sequencing analysis. Analysis of lspA-glmM genotypes identified at least 73 unrelated strains. Few mixed infections were identified, but in one case, isolates from a single biopsy exhibiting two vacA alleles were shown by lspA-glmM fingerprints to be two unrelated strains. No associated effect on ulcer disease risk was demonstrated by analysis of cagA, vacA and iceA status. Overall, the isolates of H. pylori from Argentina were similar to isolates from southern Europe or Latin American countries, and infections were associated mainly with single H. pylori strains.     

Prevalence of Helicobacter pylori vacA and cagA genotypes in Ethiopian dyspeptic patients

A total of 300 gastric biopsy samples and 50 Helicobacter pylori isolates were collected from Ethiopian adult dyspeptic patients. The vacA and cagA genes were detected in 90 and 79% of biopsy specimens, respectively, and in 100 and 87% of clinical isolates, respectively. Both genes were detected in 84% of the gastric biopsy samples and in 87% of the clinical isolates. Among vacA genotypes, the s1/m1 genotype was the most common in gastric biopsy samples (48%). The vacA and cagA positive H. pylori strains were detected to a higher degree in patients with chronic active gastritis (71%) than patients with other histopathological findings (29%) (P < 0.05).     

Association between TNF-alpha promoter polymorphism and Helicobacter pylori cagA subtype infection

AIMS: To assess the importance of tumour necrosis factor alpha (TNF-alpha) promoter polymorphism in relation to infection with the cytotoxin associated gene A (cagA) subtype of Helicobacter pylori within a dyspeptic Korean population. METHODS: Eighty three patients with gastric disease and 113 healthy controls were studied. The DNA from gastric biopsy specimens was analysed by H pylori specific and cagA specific polymerase chain reaction (PCR). To characterise TNF-alpha polymorphism at positions -308 and -238, PCR based restriction fragment length polymorphism analysis was performed. RESULTS: Helicobacter pylori infection was closely correlated with G to A transition at position -308 of the TNF-alpha promoter when compared with healthy controls (odds ratio (OR), 2.912; 95% confidence interval (CI), 1.082 to 7.836; p = 0.034). Although TNF-alpha -308 polymorphism in patients with H pylori was not significantly different from that in patients without H pylori, the -308A polymorphism was strongly associated with H pylori cagA subtype infection when compared with the polymorphism in cagA negative H pylori infection (OR, 8.757; 95% CI, 1.413 to 54.262; p = 0.019) and healthy controls (OR, 3.683; 95% CI, 1.343 to 10.101; p = 0.011). G to A genetic change at position -238 of the TNF-alpha gene was not significantly associated with H pylori cagA subtype infection. In addition, genetic polymorphisms at both sites of the TNF-alpha promoter in patients with H pylori infection did not correlate with the severity of disease. CONCLUSION: TNF-alpha -308A polymorphism was significantly related to infection with the H pylori cagA subtype in Korean patients with gastric disease.