Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan

AIM: Helicobacter pylori (H pylori ) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. The link of genotypes of H pylori to gastric cancer remains controversial. The aim of this study was to investigate the H pylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan. METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168, 74%) strains in the majority of patients. In patients with gastric cancer, the vacA s1a and s1c subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P = 0.0001 for s1a and 13/66 vs 93/168, P<0.0001 for s1c). In the middle region, the m1T strain in patients with gastric cancer was more than that of non-cancer patients (23/66 vs 33/168, P = 0.02). CONCLUSION: In Taiwan, H pylori with positive vacA s1a, cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and s1c subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.     

Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding

AIM: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from diverse geographic areas. Its association with bleeding peptic ulcer remains controversial. The aim of this study was to investigate the Helicobacter pylori vacA alleles, cagA and iceA in patients with bleeding peptic ulcer. METHODS: We enrolled patients with bleeding, non-bleeding peptic ulcers and chronic gastritis. Biopsy specimens were obtained from the antrum of the stomach for rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (60.4%) (25 patients with chronic gastritis, 26 patients with bleeding gastric ulcer, 51 patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have positive PCR results between January 2001 and December 2002. Concerning genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and ice A1 (125/278, 45%) predominated in all studied patients. In patients with bleeding peptic ulcers, vacA s1a and m1T were fewer than those in patients with non-bleeding peptic ulcers (37/106 vs 69/135, P=0.017, and 4/106 vs 21/135, P =0.002). CONCLUSION: In patients with peptic ulcers, H pylori vacA s1a and m1T prevent bleeding complication.     

Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan

AIM:Helicobacter pylori(Hpylori)has been linked to chronicgastritis,peptic ulcer,gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remainscontroversial.The aim of this study was to investigate theHpylori vacA alleles,cagA and iceA in patients with gastriccancer in Taiwan.METHODS:Patients with gastric cancer,peptic ulcer andchronic gastritis were enrolled in this study.We obtainedbiopsy specimens from the stomach at least 2 cm awayfrom the tumor margin in patients with gastric cancer,andfrom the antrum of stomach in patients with peptic ulceror chronic gastritis.DNA extraction and polymerase chainreaction were used to detect the presence or absence ofcagA and to assess the polymorphism of vacA and iceA.RESULTS:A total of 168 patients(gastric ulcer:77,duodenalulcer:66,and chronic gastritis:25)were found to havepositive PCR results of the biopsy specimens from patientswith peptic ulcer and chronic gastritis.We found positivecagA(139/168,83%),m2(84/168,50%)and iceA1(125/168,74%)strains in the majority of patients.In patients withgastric cancer,the vacA sla and slc subtypes were lesscommonly found than those in non-cancer patients(35/66 vs127/168,P=0.0001 for sla and 13/66 vs93/168,P<0.0001for slc).In the middle region,the ml T strain in patientswith gastric cancer was more than that of non-cancer patients(23/66 vs33/168,P=0.02).CONCLUSION:In Taiwan,Hpyloriwith positive vacA sla,cagA and iceAl strains are found in the majority of patientswith gastric cancer or non-cancer patients.In patients withgastric cancer,the vacA sla and slc subtypes are lessand mlT is more than in patients with peptic ulcer andchronic gastritis.     

Helicobacter pylori cagA, iceA and vacA status in Taiwanese patients with peptic ulcer and gastritis

BACKGROUND: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Different genotypes of H. pylori are confirmed from diverse geographical areas. Its association with clinical diseases remains controversial. The aim of the present study was to investigate the H. pylori vacuolating cytotoxin (vacA) alleles, cytotoxin-associated gene (cagA) and iceA, in patients with peptic ulcer and gastritis. METHODS: We enrolled patients with peptic ulcer and chronic gastritis. Biopsy specimens were obtained from the antrum and lower body of the stomach. DNA extraction and polymerase chain reaction (PCR) were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 133 patients (57 gastric ulcer, 52 duodenal ulcer, 24 chronic gastritis) had positive PCR results from biopsy specimens. Concerning genotypes, we found cagA (79% in the antrum, 92% in the body) and iceA1 (73% in the antrum, 82.8% in the body) strains in the majority of patients. The dominant vacA subtype was s1a (74.4% in the antrum, 75% in the body), followed by s1c (51.1% in the antrum, 60.5% in the body). In the middle region, the m2 strain dominated (49.6% in the antrum, 41.4% in the body), followed by m1T (19.5% in the antrum, 9.5% in the body). Mixed infection occurred in 89 patients (67%). There was no statistical difference in genotypes among the three groups. CONCLUSION: In Taiwan, H. pylori with positive cagA and iceA1 was found in the majority of cases. H. pylori with vacA s1a strains was the most common vacA subtype, followed by s1c, while s1b was rare. In the middle region, the m2 subtype was predominant followed by m1T. There was no significant association between genotypes and clinical diseases.     

vacA genotypes of Helicobacter pylori in relation to cagA status and clinical outcomes in Iranian populations

Mosaicism in vacA alleles with two distinct families of vacA signal sequences (s1 and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. Research suggests that the vacA s1 genotype is closely associated with duodenal ulcer disease and with high cytotoxin production. The aims of this study were to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, and clinical presentation in Iranian populations. Genomic DNA of biopsy specimens from patients with gastritis, peptic ulcer disease (PUD), or gastric cancer (GC) were characterized based on ureC (glmM), cagA, and vacA genotyping by using polymerase chain reaction. Of 167 patients including 33 with PUDs, 129 with non-ulcer dyspepsia (NUD), and 5 with GC, 96 (57.5%) cases were infected by Helicobacter pylori. Among these patients, H. pylori were isolated from 19 (57.7%) PUD patients, 74 (68.7%) NUD patients, and 3 (60%) GC patients. The cagA was detected in 76% of H. pylori-positive cases. The vacA s1-m2 genotype was the most prevalent in 7/19 PUD (37%) and 30/74 NUD (40.5%) patients with H. pylori infection. The prevalence of vacA s2-m1 (8%) was high in Iranian isolates. A significant association was not found between H. pylori genotypes and clinical outcomes. The vacA genotypes and cagA status were not useful markers for gastroduodenal diseases in Tehran, Iran.     

Direct determination of Helicobacter pylori vacA genotypes and cagA gene in gastric biopsies and relationship to gastrointestinal diseases

OBJECTIVE: Our aim was to detect Helicobacter pylori (H. pylori) from gastric biopsies of 248 patients using a novel, polymerase chain reaction (PCR)-based methodology, which simultaneously facilitates the determination of H. pylori vacA genotypes and cagA gene. METHODS: A simple methodology for sample preparation was established and PCR was performed with primer systems for the 16S rRNA, vacA, and cagA genes, thus circumventing the need to culture H. pylori and to extract DNA from biopsy samples. RESULTS: Infection with H. pylori was detected in 147 (59.3%) of 248 patients. The vacA signal sequence genotype s1 was present in 104 (81.3%) of 128 H. pylori-positive patients, and 24 (18.8%) patients had the genotype s2. The vacA middle region types m1 and m2 were detected in 46 (35.9%) and 79 (61.7%) patients, respectively. The combinations s1/m2 (43%) and s1/m1 (35.9%) were found more frequently than s2/m2 (18.8%). The cagA gene was detected in 75 (72.1%) of 104 H. pylori-positive biopsies with the vacA genotype s1. All 24 biopsies with the type s2 were cagA negative. Strains of the type vacA s1 were found in 97% of H. pylori-positive patients with peptic ulcer disease and were associated with the presence of the cagA gene, whereas 96% of the strains of the type vacA s2 were detected in patients who only had nonulcer dyspepsia. CONCLUSIONS: Using a novel PCR-based methodology, H. pylori 16S rRNA gene, vacA genotypes, and cagA gene can now be rapidly detected directly in gastric biopsies with high accuracy. These data demonstrate that infection with H. pylori strains of the vacA s1 genotype and the cagA gene are more likely to result in peptic ulcer disease. Determination of vacA genotypes and cagA gene may contribute to the potential clinical identification of patients at different levels of risk.     

Analysis of molecular fingerprint and virulence factors of Helicobacter pylori strains

BACKGROUND: Helicobacter pylori is now accepted as the most important agent of gastritis in humans, as well as a risk factor for peptic ulcer disease and gastric carcinoma. The outcome of the infection is related to several factors, among them bacterial ones such as cagA and vacA s1m1 genotype. Random amplified polymorphic DNA (RAPD)-PCR, has been used to generate DNA fingerprints to evaluate similarity among strains within a bacterial species. AIM: To assess the association between RAPD fingerprinting, virulence factors and the disease. METHODS: H. pylori was isolated from 112 patients (41 with gastritis; 19 with gastric ulcers; 38 with duodenal ulcer disease; and 14 with gastroesophageal reflux disease). Allelic variants of cagA and vacA were identified using the polymerase chain reaction (PCR) and the fingerprints were generated by RAPD-PCR. RESULTS: There was a strong association between the genotype vacA s1m1 and duodenal ulcers. Although RADP-PCR is a very useful tool in genotyping H. pylori, no significant correlation between the diseases studied and DNA fingerprint was detected neither with fingerprint and different vacA and, cagA genotypes. CONCLUSIONS: The extension of our analysis to patients with well-characterized gastric diseases may provide significant information on the relationship between vacA genotypes and clinical outcomes of H. pylori infection.     

Higher frequency of cagA EPIYA-C Phosphorylation Sites in H. pylori strains from first-degree relatives of gastric cancer patients

ABSTRACT: BACKGROUND: To evaluate the prevalence of more virulent H. pylori genotypes in relatives of gastric cancer patients and in patients without family histories of gastric cancer. METHODS: We evaluated prospectively the prevalence of the infection by more virulent H. pylori strains in 60 relatives of gastric cancer patients comparing the results with those obtained from 49 patients without family histories of gastric cancer. H. pylori status was determined by the urease test, histology and presence of H. pylori ureA. The cytotoxin associated gene (cagA), the cagA-EPIYA and vacuolating cytotoxin gene (vacA) were typed by PCR and the cagA EPIYA typing was confirmed by sequencing. RESULTS: The gastric cancer relatives were significant and independently more frequently colonized by H. pylori strains with higher numbers of CagA-EPIYA-C segments (OR = 4.23, 95%CI = 1.53--11.69) and with the most virulent s1m1 vacA genotype (OR = 2.80, 95%CI = 1.04--7.51). Higher numbers of EPIYA-C segments were associated with increased gastric corpus inflammation, foveolar hyperplasia and atrophy. Infection by s1m1 vacA genotype was associated with increased antral and corpus gastritis. CONCLUSIONS: We demonstrated that relatives of gastric cancer patients are more frequently colonized by the most virulent H. pylori cagA and vacA genotypes, which may contribute to increase the risk of gastric cancer.     

Significance of cagA status and vacA subtypes of Helicobacter pylori in determining gastric histopathology: virulence markers of H. pylori and histopathology

BACKGROUND: It has been suggested that Helicobacter pylori strains containing the cytotoxin-associated gene A (cagA), and s1m1 genotype of vacuolating cytotoxin gene A (vacA) may have been associated with peptic ulcer disease. The aim of the present study was to analyze such an association of cagA presence and vacA subtypes of H. pylori with histopathological findings in patients with gastritis. METHODS: Sixty-five independent H. pylori strains isolated from Turkish patients with gastritis were analyzed. The antral biopsy specimens were processed for culture and histopathology. Histopathological features were recorded and graded according to updated Sydney system. The vacA subtypes and cagA gene were tested by polymerase chain reaction. RESULTS: Mild degree of antral density was associated with mild degree of gastric neutrophil infiltration (P = 0.010). Positive cagA status correlated significantly with the presence of atrophy (P = 0.035) and neutrophil infiltration (P < 0.001), but not with H. pylori density (P = 0.754) nor the degree of mononuclear cell infiltration (P = 0.945). The vacA subtypes were independent of gastric histopathology. The odds ratios for atrophy and neutrophil infiltration of cagA+ versus cagA- strains were 3.62 (95% confidence interval [CI]: 1.04-12.66) and 53.18 (95%CI: 11.08-255.23), respectively. CONCLUSION: The presence of the cagA gene is strongly associated with atrophic and active gastritis. Distinct vacA subtypes of H. pylori appear to have no association with histopathological findings of gastritis.     

白细胞介素-1基因多态性与消化性溃疡的关系

背景：大量临床流行病学证据表明消化性溃疡发病率的地域差异与宿主免疫遗传因素密切相关,目前宿主炎症因子基因多态性与消化性溃疡的关系正受到广泛关注。目的：探讨白细胞介素（IL）-1B-511、IL-1RN基因多态性与消化性溃疡的关系。方法：选取2008年9月～2009年5月昆明医学院第一附属医院确诊的57例十二指肠溃疡（DU）、38例胃溃疡（GU）以及40例非萎缩性胃炎（NAG）患者。以快速尿素酶试验和Giemsa染色检测幽门螺杆菌（H.pylori）感染,采用PCR-RFLP检测IL-1B-511、IL-1RN基因多态性。分析IL-1基因多态性、H.pylori感染、年龄与不同疾病之间的关系。结果：NAG、DU和GU组之间H.pylori感染率、IL-1B-511、IL-1RN基因型频率的差异无统计学意义。与NAG和DU相比,年龄≥60岁是GU的危险因素（OR=5.650,95%CI：1.811～17.624;OR=3.159,95%CI：1.254～7.955）。IL-1B-511、IL-1RN基因型和H.pylori感染与消化性溃疡类型无关（P〉0.05）。结论：在昆明市,年龄≥60岁是GU的危险因素,IL-1基因多态性与消化性溃疡无关。     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment

BACKGROUND: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment. AIMS: To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome. PATIENTS: 121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively. METHODS: DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation. RESULTS: Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains. CONCLUSIONS: The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.     

Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients

BACKGROUND: Only 10-15% of all patients infected with Helicobacter pylori develop peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in the host, virulence determinants of H. pylori such as the vacuolating cytotoxin (VacA) or the cytotoxin-associated protein A (CagA) might represent a predisposition for the development of PUD. METHODS: We studied antral biopsies of 383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H. pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA gene by PCR. RESULTS: VacA genotypes and cagA status could be completely determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD, the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2 genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180 (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without gastric malignancies harbored strains with the vacA s1 genotype. The vacA genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA gene was closely associated with the vacA genotype s1 and found in 124 (88.6%) and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively, whereas strains with the genotype s2m2 were almost exclusively cagA negative. CONCLUSION: Most H. pylori strains found in patients with PUD possess the vacA s1 genotype and the cagA gene. Patients with this type of H. pylori strain but without PUD might be at higher risk of developing PUD. In contrast, the risk for PUD might be significantly decreased in those patients who are infected by H. pylori strains with the vacA s2 genotype lacking the cagA gene.     

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases

OBJECTIVE: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls. METHODS: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays. RESULTS: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies. CONCLUSIONS: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.     

Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients.

OBJECTIVES: To investigate the prevalence of the vacA, cagA, cagE, iceA, and babA2 genotypes in Helicobacter pylori strains isolated from Thai dyspeptic patients, and to determine whether any correlation exists between these genotypes and clinical manifestations. METHODS: Helicobacter pylori was examined in 112 patients (62 with non-ulcer dyspepsia (gastritis), 34 with peptic ulcer disease, and 16 with gastric cancer (GCA)), detected by culture or direct detection from gastric biopsies. Allelic variants of the vacA, cagA, cagE, iceA, and babA2 genotypes were identified by using the polymerase chain reaction. RESULTS: The positive rates for the vacAs1, vacAs2, cagA, cagE, iceA1, iceA2, and babA2 genes in H. pylori of dyspeptic patients were 100%, 0%, 98.2%, 88.4%, 45.5%, 33.1%, and 92%, respectively. The allelic variant vacAs1m1 was more prevalent (58%) than vacAs1m2 (42%). The cagA and cagE genes were commonly found together (87.5%). The most predominant genotypes were vacAs1m1, cagA, cagE, iceA1, and babA2. The various genes alone or in combination had no statistically significant association with the clinical outcomes (p>0.05). CONCLUSION: Neither single gene nor combination of vacA, cagA, cagE, iceA, and babA2 genes was significantly helpful in predicting the clinical outcome of H. pylori infection in Thai patients. The high prevalence of these genes in H. pylori isolated from Thai patient groups suggests that H. pylori strains are geographically dependent.     

Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases

BACKGROUND: Helicobacter pylori species comprise different strains, cytotoxic and non-cytotoxic, which can be identified on the basis of their genomic pattern. AIMS: (1) To evaluate the polymorphism of the vacA gene and to ascertain whether the cagA gene is present in patients with gastric adenocarcinoma. (2) To study the anti-H pylori antibody profile using western blotting. PATIENTS: Twenty one patients with gastric adenocarcinoma and 71 with H pylori associated benign disease (nine gastric ulcer, 29 duodenal ulcer, 25 antral gastritis, and eight duodenitis). METHODS: The polymerase chain reaction was used to verify the presence or absence of cagA and to study the polymorphism of vacA in gastric mucosal samples obtained during endoscopy for patients with benign diseases and at surgery for patients with gastric adenocarcinoma. Fasting sera were used to assess anti-H pylori antibodies against different H pylori antigens by western blotting. RESULTS: CagA gene and the allele s1 of vacA were significantly less frequent in patients with antral gastritis (60% and 60%) compared with patients with gastric adenocarcinoma (94% and 100%) and with other non-malignant gastroduodenal diseases (93% and 87%) (chi 2 = 16.01, p < 0.001; and chi 2 = 13.97, p < 0.01). In patients with gastric adenocarcinoma, antibodies against a 74 kDa H pylori antigen were less frequently found than in patients with benign diseases. CONCLUSIONS: H pylori infection caused by cagA positive/vacA s1 strains is a frequent finding in patients with gastric adenocarcinoma. Prospective studies are needed to confirm whether the low incidence of positive serological response to the 74 kDa H pylori antigen in patients with gastric adenocarcinoma is important.     

Helicobacter pylori Cytotoxic Genotype Is Associated With Peptic Ulcer and Influences Serology

Objective : We studied 146 patients with peptic ulcer disease (  n = 72  ), antral gastritis (  n = 58  ), or duodenitis (  n = 16  ) to ascertain whether the cytotoxic genotype of Helicobacter pylori (Hp) is associated with peptic ulcer disease and/or antral gastritis and whether it influences the circulating levels of total anti-Hp antibodies, anti- cagA antibodies, and pepsinogens. Methods : A gastric juice sample was obtained from each patient. After DNA extraction, polymerase chain reaction was used to amplify the genes urease A ( ureA ), cagA , and vacA of Hp. Results : A significant association was found between peptic ulcer disease and the cytotoxic genotypes, characterized by the presence of s1 and m1 alleles of vacA and by cagA. Patients with a cagA -positive genotype showed a significant increase in anti- cagA antibodies and also had significantly increased circulating levels of pepsinogen C. Conclusions : Cytotoxic Hp strains are mainly involved in determining peptic ulcer disease, but not antral gastritis. The higher levels of circulating pepsinogen C found in patients infected with cytotoxic genotypes may reflect the higher degree of inflammation sustained by these strains.     

IL-1β (+3953 C/T) and IL-8 (-251 A/T) Gene Polymorphisms in H. pylori Mediated Gastric Disorders

Background: Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. Objective: The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population. Methods: One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori (control group) were studied for the association between IL-1β (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylorimediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP-PCR. Results: Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H pylori+ non-ulcerative gastritis+, H. pylori+ ulcerative gastritis+ and H. pylori- non-ulcerative gastritis+. A significantly higher frequency of TT genotype (p=0.02) in IL-1β +3953 in H. pylori+ ulcerative gastritis+ was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 (-251A/T) were found among the patients. Conclusion: The data suggest that TT genotype in IL-1β +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations.     

Relationship between Helicobacter pylori hopQ genotype and clinical outcome in Asian and Western populations

Background and Aims:  Outer membrane proteins of Helicobacter pylori mediate important pathogen–host interactions such as colonization, adhesion and the inflammatory response. hopQ genotypes have been suggested to be associated with increased risk of peptic ulcer. The aim of this study was to test the relation of hopQ genotype to H. pylori -related disease and histological changes in Asian and Western countries.
Methods:  hopQ genotype, cagA status and vacA genotype of H. pylori isolated from patients from Asian and Western countries were determined and the results were compared with the clinical presentation and gastric histology.
Results:  Most Asian strains possessed virulent genotypes ( hopQ type I, vacA s1-m1 and cagA -positive). In Western countries, hopQ type I genotype was significantly linked with vacA s1 and m1 genotypes and cagA -positive status. Inflammatory cell infiltration and atrophy scores were significantly higher in patients with hopQ type I strains than those with type II in Western patients. However, the hopQ type I genotype was not associated with an increased risk for peptic ulcer or gastric cancer, and had no additive effects to vacA genotypes or cagA -positive status.
Conclusion:  The expression of multiple putative virulence factors in Asian strains likely explains the relatively high incidence of clinical outcomes including gastric cancer compared with other parts of the world. Although hopQ genotype did not improve the predictive value above other genotyping for development of H. pylori -related gastroduodenal diseases, the hopQ genotype might be able to add a useful virulence marker for gastroduodenal diseases.