Analysis of the relationship between oipA, babA2, babB genotypes and helicobacter pylori-related gastric precancerous lesions.

OBJECTIVE: To investigate the distribution of helicobacter pylori-related genotypes of oipA, babA2, and babB in patients with gastrointestinal diseases. Methods: The retrospective study was conducted at the Jiamusi College, Heilongjiang University of Traditional Chinese Medicine, Harbin, China, and comprised data from February 2017 to May 2020 of patients of either gender 20-80 years who underwent gastroscopy. An instrument based on polymerase chain reaction was used to amplify oipA, babA2 and babB genes, and their distribution in terms of gender, age and pathological types was analysed. RESULTS: Among the 116 patients, 52(44.8%) had oipA genotype, 48(41.2%) babA2, and 72 (62.1%) babB, respectively, and the size of amplified products of 486bp, 219bp and 362bp, respectively. The infection rate of oipA and babB genotypes was highest [26(50.0%) and 31(43.1%)]in those aged 61-80 years, and lowest [9(17.3%) and 15(20.8%)]in those aged 20-40 years. The infection rate of babA2 genotype was highest [23(47.9%)] in those aged 41-60 years, and lowest [12(25.0%)] in those aged 61-80 years. Male patients were under a higher [28(53.9%) and 26(54.2%)] rate of infection with oipA and babA2, and female patients has a higher [40(55.6%)] rate of infection with babB. Among Hp-infected patients with digestive diseases, babB genotype was mainly found in patients with chronic superficial gastritis[17(58.6%)], duodenal ulcer[17(85.0%)], chronic atrophic gastritis[19(59.4%)] and gastric ulcer[16(72.7%)], while oipA genotype was mainly found in patients with gastric cancer[8(61.5%)]. CONCLUSIONS: Chronic superficial gastritis, duodenal ulcer, chronic atrophic gastritis, and gastric ulcer may have a close bearing on babB genotype infection, while oipA genotype infection may be associated with gastric cancer.

Detection of the babA2 adhesin protein gene in Helicobacter pylori clinical isolates.

The study compared the effectiveness of two different primer sets for detecting and evaluating the prevalence of the babA2 gene in 52 H. pylori clinical isolates from patients with chronic gastritis (n=32), duodenal ulcer (n=16) and stomach cancer (n=4) in St. Petersburg, Russia. The PCR was used for detection of the babA2 gene with 271 bp and 832 bp primer sets followed by sequencing of the PCR-amplicons. The largest proportion of babA2-positive strains - 90.4% (47/52) was detected using a 271 bp PCR primer set. Detection of the 832 bp PCR positive samples was observed only in 51.9% of cases (27/52). The largest proportion of babA2-positive strains - 90.4% (47/52) was detected using 271 bp PCR primer set; detection of 832 bp PCR product was observed only in 51.9% cases (27/52), however, there were no significant differences in the babA2 gene detection rates (p>0.05). Bioinformatic analysis revealed a homology of Sanger sequenced PCR products 271 bp and 832 bp of babA2 gene with regions of the babA2, babA1, and chimeric babA/B genes of H. pylori strains annotated in the NCBI database. Regardless of the primer set used, the presence of babA2 was not significantly associated with duodenal ulcer nor gastric cancer (p>0.05). The combination of the three babA2, cagA, and vacAs1 genes did not reveal any association between the presence of babA2 gene and cagA/vacAs1 genes in H. pylori strains (p>0.05). Thus, none of the two primer sets (271 bp and 832 bp) appears sufficiently informative for detecting the babA2 gene to assess virulence of H. pylori Russian strains.

Increased Risk of Severe Gastric Symptoms by Virulence Factors vacAs1c, alpA, babA2, and hopZ in Helicobacter pylori Infection.

Two virulence factors of Helicobacter pylori, cagA and vacA, have been known to play a role in the development of severe gastric symptoms. However, they are not always associated with peptic ulcer or gastric cancer. To predict the disease outcome more accurately, it is necessary to understand the risk of severe symptoms linked to other virulence factors. Several other virulence factors of H. pylori have also been reported to be associated with disease outcomes, although there are many controversial descriptions. H. pylori isolates from Koreans may be useful in evaluating the relevance of other virulence factors to clinical symptoms of gastric diseases because the majority of Koreans are infected by toxigenic strains of H. pylori bearing cagA and vacA. In this study, a total of 116 H. pylori strains from Korean patients with chronic gastritis, peptic ulcers, and gastric cancers were genotyped. The presence of virulence factors vacAs1c, alpA, babA2, hopZ, and the extremely strong vacuolating toxin was found to contribute significantly to the development of severe gastric symptoms. The genotype combination vacAs1c/alpA/babA2 was the most predictable determinant for the development of severe symptoms, and the presence of babA2 was found to be the most critical factor. This study provides important information on the virulence factors that contribute to the development of severe gastric symptoms and will assist in predicting clinical disease outcomes due to H. pylori infection.

Association of Helicobacter pylori babA2 gene and gastric cancer risk: a meta-analysis.

BACKGROUND: The association of Helicobacter pylori (H. pylori) babA2 gene with gastric cancer (GC) was reported by several studies, but results were inconsistent. This meta-analysis was performed to investigate the relationship between H. pylori babA2 gene and GC risk. METHODS: Case-control studies involving the association between H. pylori babA2 gene and GC risk were systematically identified from PubMed databases. A meta-analysis was used to pool studies and to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of H. pylori babA2 gene associated with GC risk. RESULTS: Twenty studies were identified with a total of 1289 GC cases and 1081 controls. H. pylori babA2 gene was associated with an increased risk of GC by 2.05 fold (95% CI, 1.30-3.24, P = 0.002). In subgroup analysis, we found that H. pylori babA2 gene was significantly associated with GC risk in Asian population (OR = 2.63, 95% CI: 1.36-5.09 P = 0.004) but not in South American population (OR = 1.35, 95% CI: 0.69-2.64, P = 0.379). CONCLUSIONS: This meta-analysis indicates that H. pylori babA2 gene may be associated with increased risk of GC, especially in Asian population.

Blood group antigen-Binding Adhesion2 (BabA2) gene in gastric tissue biopsies as a diagnostic biomarker for Helicobacter pylori infection.

BACKGROUND: The Lewis (b) blood group antigen-Binding Adhesion2 (BabA2) has been reported to mediate the attachment of H. pylori to human. AIM: assessment the diagnostic potential of detection of (BabA2) gene compared with immunostaining of Lewis (b) by specific mouse monoclonal antibodies in gastric biopsies from Egyptian Patients as a diagnostic maker for Helicobacter pylori infection. MATERIALS AND METHODS: Fifty untreated patients suffering from dyspeptic complaints were enrolled in this study and underwent for upper gastro-duodenal endoscopy. Biopsies were taken for histological examination by (H&E) and immunohistochemical analysis for Lewis b by specific mouse monoclonal antibodies, and scoring of Lewis b expression in gastric tissue biopsy as well as molecular detection of BabA2 gene of H. pylori by PCR. Biochemical analysis was performed to detect the presence of H. pylori urease activity using Rapid Urease Test (RUT). RESULTS: Out of 50 gastric biopsies, 41 biopsies were positive for histological, Immunostaining for Lewis b expression and urease activity test (RUT) for H pylori. RUT showed a sensitivity of 87.8%, specificity 88.9%, positive predictive value (PPV) 97.2%, and negative predictive value (NPV) 61.5%. BabA2 gene results revealed that, out of 41 positive biopsied cases, 39 (95.1%) were positive by the PCR test for BabA2 gene. And all 9 negative biopsies (100%) for H pylori negative for BabA2gene so the sensitivity and specificity of BabA2 gene detection in gastric biopsies by PCR were 95.1% and 100%; respectively. CONCLUSION: BabA2 gene detection in gastric tissue biopsies could be suggested as a diagnostic biomarker to be included among the other biomarkers routinely performed for clinical diagnosis of H. pylori infection.

Helicobacter pylori vacA s1m1 genotype but not cagA or babA2 increase the risk of ulcer and gastric cancer in patients from Southern Mexico.

BACKGROUND: The vacA, cagA and babA2 genotypes of Helicobacter pylori are associated with gastric pathology. The objectives were to determine the frequency of infection and distribution of the vacA, cagA and babA2 genotypes of H. pylori in patients with gastric ulcer, chronic gastritis and gastric cancer, and to evaluate the association of virulent genotypes with diagnosis. METHODS: We studied 921 patients with symptoms of dyspepsia or with presumptive diagnosis of gastric cancer. The DNA of H. pylori and the vacA, cagA and babA2 genes was detected by PCR in total DNA from gastric biopsies. The association of H. pylori and of its cagA, vacA and babA2 genotypes with diagnosis was determined by calculating the odds ratio (OR). RESULTS: Chronic gastritis was confirmed in 767 patients, gastric ulcer in 115 and cancer in 39. The prevalence of H. pylori was 47.8, 49.6 and 61.5% in those groups, respectively. H. pylori was more frequent in the surrounding tissue (69.2%) than in the tumor (53.8%). The vacA s1m1 genotype predominated in the three groups (45.2, 61.4 and 83.3%, respectively). H. pylori was associated with cancer (ORadjusted = 2.08; 95% CI 1.05-4.13; p = 0.035) but not with ulcer (ORadjusted = 1.07; 95% CI 0.71-1.61; p = 0.728). The s1m1 genotype was associated with ulcer and cancer (ORadjusted = 2.02; 95% CI 1.12-3.62; p = 0.019 and ORadjusted = 6.58; 95% CI 2.15-20.08; p = 0.001, respectively). babA2 was associated with gastric cancer, and cagA was not associated with the diagnosis. CONCLUSIONS: In population from Southern Mexico, H. pylori and the s1m1 genotype were associated with gastric cancer and the s1m1/cagA+/babA2+ strains predominated in tumor and adjacent tissue.

Helicobacter pylori strains harboring babA2 from Indian sub population are associated with increased virulence in ex vivo study.

BACKGROUND: The babA2 gene along with the cagA and vacA of Helicobacter pylori has been considered as a risk factor for the disease outcome in certain populations. This study was aimed to understand the role of babA2 of H. pylori with the background of cagA and vacA in disease manifestations in Indian sub population. METHODS: A total of 114 H. pylori strains isolated from duodenal ulcer (DU) (n = 53) and non-ulcer dyspepsia (NUD) patients (n = 61) were screened for the prevalence of these virulence markers by PCR. The comparative study of IL-8 production and apoptosis were done by co-culturing the AGS cell line with H. pylori strains with different genotypes. Adherence assay was performed with babA2 positive and negative strains. Two isogenic mutants of babA2 were constructed and the aforesaid comparative studies were carried out. RESULTS: PCR results indicated that 90.6 % (48/53), 82 % (50/61) and 73.6 % (39/53) strains from DU patients were positive for cagA, vacA, and babA2, respectively. Whereas the prevalence of these genes in NUD subjects were 70.5 % (43/61); 69.8 % (37/53), and 65.6 % (39/61), respectively. Although adherence to AGS cells was comparable among strains with babA2 positive and negative genotypes, but the triple positive strains could induce highest degree of IL-8 production and apoptosis, followed by the cagA (-)/vacA (-)/babA2 (+) strains and triple negative strains, respectively. The wild type strains showed significantly higher IL-8 induction as well as apoptosis in ex vivo than its isogenic mutant of babA2. CONCLUSION: PCR study demonstrated that there was no significant association between the distribution of babA2 genotype or of triple positive strains and disease outcome in this sub population. The adherence assay showed that there was no significant difference in the extent of adherence to AGS cells among babA2 positive and negative strains. But the ex vivo study indicated that the triple positive or even the babA2 only positive strains are involved in increased virulence. The wild type strains also exhibited increased virulence compared to the babA2 mutant strains. This inconsistency demonstrated that bacterial genotype along with host genetic polymorphisms or other factors play important role in determining the clinical manifestation of H. pylori infections.

Helicobacter pylori vacA i region polymorphism but not babA2 status associated to gastric cancer risk in northwestern Iran.

Helicobacter pylori-specific genotypes have been strongly associated with an increased risk of gastric cancer (GC). The aim of the present work was to study the associations of H. pylori virulence factors, vacA i region polymorphisms and babA2 status with GC risk in Azerbaijan patients. The DNA extracted from gastric biopsy specimens was used to access the babA2 and vacA genotypes. Overall, babA2 was present in 85.39 % (76/89) of H. pylori strains: 19 out of 24 (79.16 %) strains from GC, 16 out of 17 (94.14 %) strains from peptic ulcer disease (PUD) and 41 out of 48 (85.14 %) strains from chronic gastritis. No significant association was found between babA2 genotype and clinical outcomes (P > 0.05). i1 vacA polymorphism was detected in 46/89 (51.68 %) strains: in 21/24 (87.5 %), 6/17 (35.29 %) and 19/48 (39.58 %) patients with GC, PUD and chronic gastritis, respectively. i2 allele was detected in 43 (48.31 %) out of all 89 strains examined: 3 (14.28 %) of 24 strains from GC, 11 (64.71 %) of 17 from PUD, and 29 (60.42 %) of 48 strains from chronic gastritis. In this study, multiple linear regression analysis confirmed the strong association of i1 allele with GC (partial regression correlation 0.455 ± 0.101; P = 0). Results of multiple logistic regression analysis showed that vacA i1 genotype was significantly associated with GC compared with a control group (gastritis) (odds ratio 13.142, 95 % CI 3.116-55.430; P = 0). Findings from the measurement of H. pylori babA2 and vacA genotypes indicate a strong correlation between the vacA i1 allele and GC risk in the Azerbaijan area of Iran.

Clinical and Histopathological Relevance of Helicobacter pylori BabA2 Genotype

Introduction: H. pylori BabA is an outer membrane protein that mediates bacterial adherence to the gastric epithelium, triggers several pathways during the course of infection, and thus contributes to the disease development. Considering the variability in the presence of BabA coding gene (babA2) among H. pylori clinical strains, the aim of this study was to assess the relationship between the genotype status of H. pylori babA2 and the severity of clinical and histopathological outcomes. Methods: Gastric mucosal biopsy specimens were collected from 30 CLO test-positive patients, 16 with gastritis and 14 with peptic ulcer disease. Polymerase chain reaction was carried out to detect the presence of H. pylori-specific glmM gene and BabA coding gene (babA2). Histopathological examination was performed to evaluate the severity of H. pylori-associated gastric disease according to the Updated Sydney Classification System. Results: The glmM and babA2 genes were present in 100% and 86.7% of the tested H. pylori strains, respectively. Although higher degrees of inflammatory activity and H. pylori density were noted in babA2-positive biopsy specimens, there was no statistically significant association between babA2 genotype status and the severity of gastric disease. Conclusion: The babA2 genotype status of H. pylori may not be considered as a sole marker for determining the infection outcomes.

Analysis of the genotypic diversity of strains of Helicobacter pylori isolated from pediatric patients in Mexico.

Genotypic differences in Helicobacter pylori play an important role in infection. We characterized the diversity of the cagA, cagE, babA2, and vacA genes in H. pylori strains isolated from pediatric patients and the relationship between these genes and clinical disease. Additionally, we employed the Neighbor-net algorithm to predict the behavior of the genotypes of the strains isolated from patients. Of 93 patients analyzed, 32 were positive for infection. A total of 160 H. pylori strains (five isolates per positive patient) were analyzed. A total of 91% and 83% of strains possessed the cagA and cagE genes, respectively. For the vacA gene, 84% of strains possessed the s1 allele, 15% the s2 allele, 81% the m1 allele and 13.8% the m2 allele. The babA2 gene was present in 79% of strains. Infection with H. pylori strains with the vacA (s1m1) genotype was associated with risk of esophagitis and gastritis (p=0.0001). The combination of cagA and vacA (s1m1) was significantly associated with abdominal pain (p=0.002); however, EPIYA type was not significantly associated with abdominal pain. A total of 16 different genotypes were identified; the most common genotype was vacAs1m1cagA+cagE+babA2+ (47.5%). A total of 84% of pediatric patients were infected by at least two and up to five different genotypes. The network recovered two genotype groups (A: strains with vacAs1 and B: strains with vacAs2). The presence of multiple paths in the network suggests that reticulate events, such as recombination or reinfection, have contributed to the observed genotypic diversity.

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer.

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori-infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this meta-analysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.

Association between Genotypes and Gastric Mucosal Lymphocytes in Helicobacter pylori-infected Children / 대한소아소화기영양학회지

PURPOSE: Helicobacter pylori infection is probably acquired in childhood and persists as an asymptomatic infection for decades in most individuals. It is unclear why only a minority of those infected develop a clinical manifestation, even in childhood, such as peptic ulcer disease. H. pylori infection activates local immune responses and causes lymphocyte infiltration in the gastric mucosa. We have previously reported that both T and B cells in the lamina propria play important roles in the local immune response of H. pylori-infected children. The aim of this study was to investigate the association between H. pylori genotypes and gastric mucosal lymphocytes. METHODS: Twenty-five H. pylori-infected children (10 with peptic ulcer disease and 15 with gastritis) were enrolled in this study. We investigated the genotypes (cagA, cagE, vacA, and babA2) and evaluated the association with clinical manifestations, histopathology, and gastric mucosal lymphocytes. RESULTS: The prevalence of cagA, cagE, vacA s1m1, and babA2 was 80%, 60%, 84%, and 88%, respectively. The most prevalent (68%) combination of cagA, vacA, and babA2 genotypes was cagA+/ vacA s1m1+/babA2+. H. pylori genotypes were not associated with clinical manifestations, histopathology, or gastric mucosal lymphocytes. CONCLUSION: There was no association between the cagA, cagE, vacA, or babA2 status and gastric mucosal lymphocytes. The role of the host immune response in relation to H. pylori genotypes and disease potential in children needs further studies.

No influence of Lewis B expression in Helicobacter pylori on bacterial adhesion property / 中华消化杂志

Objective To investigate the possible influence of Lewis B expression in Helicobacter pylori (H.pylori) on bacterial adhesion property, and determine the relationship between babA 2 gene in H.pylori and peptic ulcer. Methods The bacterial adhesion property in a total of 78 H.pylori strains was performed using adherence assay in vitro, and the frequency of babA 2 gene was determined by polymerase chain reaction (PCR). Results Among 47 H.pylori strains isolated from peptic ulcer patients, 18 (38.3%) were positive for babA 2 gene, while babA 2 was positive in 14 (45.2%) of 31 strains isolated from non ulcer dyspepsia patients ( P =0.427). Among 31 H.pylori strains expressing Lewis B, 24 (77.4%) were positive for adherence assay, compared with 38 (80.9%) of 47 H.pylori strains without expression of Lewis B ( P =0.463). Conclusions (1) There is no association between babA 2 status in H.pylori strain and peptic ulcer in our population; (2) The expression of Lewis B in H.pylori does not interfere with bacterial adhesion property, and thus supports that the gastric epithelium is the receptor for Lewis B of H.pylori.

Helicobacter pylori iceA and babA2 genotype and its clinical association in Shanghai area / 中华消化杂志

Objective To determine the distribution of Helicobacter pylori (H.pylori) iceA, babA2 in patients in Shanghai and explore the association of H. pylori strain genotype with its clinical outcome after infection. Methods A total of 141 H. pylori strains was isolated from gastric biopsy samples of 43 patients with chronic gastritis, 47 patients with duodenal ulcer (DU), 30 patients with gastric ulcer(GU) and 21 patients with non cardia gastric carcinoma. The iceA, vacA, cagA, and babA2 genotypes were determined by polymerase chain reaction (PCR). Results iceA1, iceA2 and babA2 were detected in 74.5% (105/141) , 15.6% (22/141) and 63.8% (90/141) of the 141 H.pylori strains, respectively, while 2 of isolated H. pylori strain (1.4%) were positive for both iceA alleles and 16(11.3%) were negative for both iceA alleles. The prevalence of babA2 and the combined genotype of babA2 and cagA in H. pylori isolated from DU patients were significantly higher than that in GU patients (74.5% vs. 50.0% for babA2, P =0.028; 70.2% vs. 46.7% for babA2 and cagA, P =0.039). There was no significant difference in prevalence of babA2 among other disease groups. No association of different clinical diseases with iceA genotype was detected. Conclusions The most common genotype of H.pylori strains isolated from patients in Shanghai is iceA1 +/babA2 +. babA2 may play different role in the pathogenesis of duodenal ulcer and gastric ulcer. No association between iceA status and clinical outcome of H.pylori infection was confirmed in our study.