cagA Strains Research Articles

Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand.

Gastric cancer risk is varied among different regions of Thailand. We examined the characteristics of Helicobacter pylori infection in two regions of Thailand. The H. pylori status of 273 dyspeptic patients (136 from the South and 137 from the North; a low and high incidence of gastric cancer region, respectively) was evaluated, and virulence genotypes (cagA, vacA, hrgA and jhp0562-positive/β-(1,3)galT) were determined. The overall H. pylori infection rate was 34.1% (93/273). The prevalence was higher in the North than in the South (50.4% vs. 17.6%, P <0.001) and was significantly higher among individuals with the following characteristics: low income, birthplace in the Northeast or North regions, agricultural employment, or consumption of alcohol or unboiling water. Among these socio-demographic determinants, region was an independent risk factor for H. pylori infection (odds ratio = 6.37). Patients including both H. pylori infected and uninfected cases who lived in the North had significantly more severe histological scores than those in the South. In contrast, among H. pylori-positive cases, patients in the South had significantly more severe histological scores than those in the North. Of the 74 strains cultured, 56.8% carried Western-type cagA, with a higher proportion in the South than in the North (76.2% vs. 49.1%, P = 0.05). In disagreement with the current consensus, patients infected with the Western-type cagA strains had more severe inflammation scores in the antrum than those infected with the East Asian-type cagA strains (P = 0.027). Moreover, Western-type cagA strains induced more severe histological scores in patients from the South than those of either genotype from the North. Other virulence genes had no influence on histological scores. The incidence of gastric cancer in Thailand was different among regions and corresponded to differences in the prevalence of H. pylori infection. More careful follow-up for patients in the South will be required, even if they are infected with H. pylori carrying Western-type cagA.

Helicobacter pylori virulence genes of minor ethnic groups in North Thailand

BackgroundThere are few studies analyzed concurrently the prevalence and genotypes of Helicobacter pylori infection with the ancestor origins from different ethnics, especially with including minority groups. We recruited a total of 289 patients in MaeSot, Thailand (154 Thai, 14 Thai-Chinese, 29 Karen and 92 Hmong ethnics). The virulence genes and genealogy of the strains were determined by PCR-based sequencing.ResultsBased on culture and histology/immunohistochemistry, the prevalence of H. pylori infection was 54.5% (158/289). Among 152 isolates cultured, the East-Asian-type cagA was predominant genotype among strains from Hmong, Thai-Chinese and Thai (96.0% [48/50], 85.7% [6/7] and 62.7% [47/75], respectively), whilst majority of strains from Karen had Western-type cagA (73.3% [11/15]). Patients infected with the East-Asian-type cagA strains had significantly higher activity and intestinal metaplasia in the antrum and activity in the corpus than those with Western-type cagA (P = 0.024, 0.006 and 0.005, respectively). The multilocus sequencing typing analysis discriminated that most strains from Hmong and Thai-Chinese belonged to hspEAsia (92.0 and 85.7%, respectively), whereas strains from Karen predominantly possessed hpAsia2 (86.7%) and strains from Thai were classified into hspEAsia (45.2%) and hpAsia2 (31.1%).ConclusionsHelicobacter pylori genotypes were relatively different among ethnic groups in Thailand and were associated with the source of ancestor even living in a small rural town. Caution and careful check-up are required especially on Hmong ethnic associated with high prevalence of virulence genotypes of H. pylori.

Helicobacter pylori cagA and vacA genes in dyspeptic Ghanaian patients

BackgroundHelicobacter pylori infection is prevalent in Ghana. The development of gastro-duodenal disease is dependent on virulence of the infecting strain, host susceptibility and environmental factors. Helicobacter pylori cagA and vacA strains induce more inflammation, ulceration and oncogenesis. Here, for the first time we present data on H. pylori cagA and vacA genes and their association with gastro-duodenal disease in Ghana. A total of 159 patients with dyspepsia at Korle-Bu Teaching Hospital, Accra, were investigated for H. pylori with urease-CLO, of which 113 (71.1%) were positive. Genomic DNA was extracted from antral biopsies using QIAGEN DNeasy kit. Detection of H. pylori vacA and cagA genes were determined by PCR as previously described.ResultsIn total, 110 (69.2%) vacAs1, 71 (44.7%) vacAm1, 35 (22.0%) vacAm2, 77 (48.4%) cagA-(hydrophilic region) and 109 (68.6%) cagA-(internal duplication region) were detected. In multivariate analysis, duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) (OR 3.1 CI 1.2–7.9) or vacAs1m1 (OR 6.5 CI 1.2–34.0).ConclusionsMajority of biopsies were colonized with H. pylori harboring both cagA and vacA. H. pylori cagA-(internal duplication region) was more prevalent than cagA-(hydrophilic region). Duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) or vacAs1m1.

English

cagA gene, a marker for the cag pathogenicity island (CagPAI) and a virulent factor in Helicobacter pylori infection codes for 120 to 145 kDa protein that is associated with cytotoxin production and more severe clinical outcomes. The aim of this study was to determine whether any correlation exists between H. pylori CagA protein and the endoscopic findings among dyspeptic patients from South-western, Nigeria and also to investigate the evolutionary relationships among H. pylori cagA gene with the GenBank strains. A total of one hundred and twenty four H. pylori positive isolates were amplified for the detection of cagA by polymerase chain reaction (PCR) and H. pylori isolates positive for cagA were further evaluated for protein expression using western blotting analysis. Also, DNA sequencing, blasting and phylogenetic analysis were performed on twelve selected isolates positive for cagA. cagA gene was detected in all the 124 samples (100%) and protein expressions of cagA by western blotting analysis was 88.7% (110/124). There was a high prevalence (91.7%) of expressed cagA strains in patients with positive endoscopic lesions than those with normal endoscopic findings (85.7%); however, association was not statistically significant (P&gt;0.05). Also, the expressed cagA had no statistically significant association with all the positive endoscopic findings (P&gt;0.05). Phylogenetic analysis of the selected H. pylori cagA gene showed high similarity with some GenBank strains of western cagA H. pylori. This study shows that CagA is high among dyspeptic patients in Nigeria but with no statistically significant association with the endoscopic findings. Key words: Protein expression, CagA, protein, GenBank, dyspeptic.&nbsp

Helicobacter pylori cytotoxin-associated gene A genotype in Egyptian patients with Parkinson’s disease: could eradication benefit?

Strong growing evidence supports a link between Helicobacter pylori (HP) infections and Parkinson’s disease (PD). The purpose of this study was to explore the association between infection with HP cytotoxin-associated gene A (cagA) genotype and PD in Egyptian patients and the influence of its eradication on pharmacokinetic and clinical response to l-dopa. This study was performed on 87 idiopathic PD patients and 45 age- and sex-matched controls. HP infection was diagnosed with HP stool antigen test and HP cagA genotype was detected by PCR. PD patients were subjected to UCLA parkinsonism scale, Hoehn and Yahr staging, and l-dopa plasma level detection by high-performance liquid chromatography. HP PD patients were divided into eradicated group (received standard anti-HP therapy) and placebo group (received antioxidant therapy). Four weeks after therapy, patients were reevaluated. Among PD patients, frequency of HP infection was significantly higher than controls (55.2 vs 33.3%, P = 0.02), especially with HP cagA strain (81.2 vs 40%, P = 0.002). PD was more severe in HP infected (P < 0.001), especially in HP cagA-positive patients (P = 0.04) with significant lower l-dopa plasma levels (P < 0.001). cagA strains were associated with higher risk of increased PD severity (OR, 2.139; P = 0.029). Opposing antioxidant therapy, HP eradication treatment improved PD severity (UCLA score decreases by 30%) and increased l-dopa level by 40%. There is a proved link between PD and infection with virulent HP cagA strains. HP could affect l-dopa level by mechanisms other than reactive oxygen radical’s production which need further evaluation.

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.

Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.

Mo1235 Helicobacter pylori Virulence Genes of Minor Ethnic Groups in North Thailand

Background There are few studies analyzed concurrently the prevalence and genotypes of Helicobacter pylori infection with the ancestor origins from different ethnics, especially with including minority groups. We recruited a total of 289 patients in MaeSot, Thailand (154 Thai, 14 Thai-Chinese, 29 Karen and 92 Hmong ethnics). The virulence genes and genealogy of the strains were determined by PCR-based sequencing. Results Based on culture and histology/immunohistochemistry, the prevalence of H. pylori infection was 54.5% (158/289). Among 152 isolates cultured, the East-Asian-type cagA was predominant genotype among strains from Hmong, Thai-Chinese and Thai (96.0% [48/50], 85.7% [6/7] and 62.7% [47/75], respectively), whilst majority of strains from Karen had Western-type cagA (73.3% [11/15]). Patients infected with the East-Asian-type cagA strains had significantly higher activity and intestinal metaplasia in the antrum and activity in the corpus than those with Western-type cagA (P = 0.024, 0.006 and 0.005, respectively). The multilocus sequencing typing analysis discriminated that most strains from Hmong and Thai-Chinese belonged to hspEAsia (92.0 and 85.7%, respectively), whereas strains from Karen predominantly possessed hpAsia2 (86.7%) and strains from Thai were classified into hspEAsia (45.2%) and hpAsia2 (31.1%). Conclusions Helicobacter pylori genotypes were relatively different among ethnic groups in Thailand and were associated with the source of ancestor even living in a small rural town. Caution and careful check-up are required especially on Hmong ethnic associated with high prevalence of virulence genotypes of H. pylori.

Helicobacter pylori-Mediated Protection from Allergy Is Associated with IL-10-Secreting Peripheral Blood Regulatory T Cells.

Helicobacter pylori infections are usually established in early childhood and continuously stimulate immunity, including T-helper 1 (Th1), Th17, and regulatory T-cell (Treg) responses, throughout life. Although known to be the major cause of peptic ulcer disease and gastric cancer, disease occurs in a minority of those who are infected. Recently, there has been much interest in beneficial effects arising from infection with this pathogen. Published data robustly show that the infection is protective against asthma in mouse models. Epidemiological studies show that H. pylori is inversely associated with human allergy and asthma, but there is a paucity of mechanistic data to explain this. Since Th1 and Treg responses are reported to protect against allergic responses, we investigated if there were links between the human systemic Th1 and Treg response to H. pylori and allergen-specific IgE levels. The human cytokine and T-cell responses were examined using peripheral blood mononuclear cells (PBMCs) from 49 infected and 58 uninfected adult patients. Concentrations of total and allergen-specific plasma IgE were determined by ELISA and ImmunoCAP assays. These responses were analyzed according to major virulence factor genotypes of the patients’ colonizing H. pylori strains. An in vitro assay was employed, using PBMCs from infected and uninfected donors, to determine the role of Treg cytokines in the suppression of IgE. Significantly higher frequencies of IL-10-secreting CD4+CD25hi Tregs, but not H. pylori-specific Th1 cells, were present in the peripheral blood of infected patients. Total and allergen-specific IgE concentrations were lower when there was a strong Treg response, and blocking IL-10 in vitro dramatically restored IgE responses. IgE concentrations were also significantly lower when patients were infected with CagA+ strains or those expressing the more active i1 form of VacA. The systemic IL-10+ Treg response is therefore likely to play a role in H. pylori-mediated protection against allergy in humans.

Prevalence of cagA and babA2 positive Helicobacter pylori strains in dyspeptic patients in Iran

Background: Helicobacter pylori genome encodes a large number of virulence and adhesion factors that involved in bacterial adhesion to host cells and exerts its virulence effect with CagA secretion. In this study, we aimed to examine the relationships between babA2 and cagA genotype and presence of gastric disorders in patients from Iran. Material and Methods: The presence of H. pylori and selected genes ( cagA and babA2 ) were detected by PCR method from the genomic DNA of 105 patients who had been diagnosed with gastric disorders like chronic gastritis by endoscopic and histopathologic routes. Results: Presence of H. pylori ( glmM gene ) was detected in 85 out of 105 (80.9%) patients. According to our results cagA gene was found in 66 out of 85 (77.6%) patients and babA2 gene was found in 80 out of 85 (94.1%) patient. Conclusion: In conclusion, the cagA and babA2 genotypes might be considered as useful biomarkers for non-ulcer disease (NUD) patients and gastric disorders in the geographic region of Iran and the presence of H. pylori strains with double-positive status is high clinical relevance to H. pylori -associated diseases.

On the importance of developing a new generation of breath tests for Helicobacter pylori detection

State-of-the-art methods for non-invasive detection of the Helicobacter pylori (H. pylori) infection have been considered. A reported global tendency towards a non-decreasing prevalence of H. pylori worldwide could be co-influenced by the functional limitations of urea breath tests (UBTs), currently preferred for the non-invasive recognition of H. pylori in a clinical setting. Namely, the UBTs can demonstrate false-positive or false-negative results. Within this context, limitations of conventional clinically exploited H. pylori tests have been discussed to justify the existing need for the development of a new generation of breath tests for the detection of H. pylori and the differentiation of pathogenic and non-pathogenic strains of the bacterium. This paper presents the results of a pilot clinical study aimed at evaluating the development and diagnostic potential of a new method based on the detection of the non-urease products of H. pylori vital activity in exhaled gas. The characteristics of breath of adolescents with H. pylori-positive and H. pylori-negative functional dyspepsia, together with a consideration of the cytotoxin-associated gene A (CagA) status of H. pylori-positive subjects, have been determined for the first time using innovative point-contact nanosensor devices based on salts of the organic conductor tetracyanoquinodimethane (TCNQ). The clinical and diagnostic relevance of the response curves of the point-contact sensors was assessed. It was found that the recovery time of the point-contact sensors has a diagnostic value for differentiation of the H. pylori-associated peptic ulcer disease. The diagnostically significant elongation of the recovery time was even more pronounced in patients infected with CagA-positive H. pylori strains compared to the CagA-negative patients. Taking into account the operation of the point-contact sensors in the real-time mode, the obtained results are essential prerequisites for the development of a fast and portable breath test for non-invasive detection of cytotoxic CagA strains of H. pylori infection. The relaxation time of the point-contact nanosensors could be selected as a diagnostic criterion for non-invasive determination of H. pylori-associated destructive lesions of the gastroduodenal area in adolescents, using the point-contact spectroscopic concept of breath analysis. This can subsequently be implemented into a ‘test-and-treat’ approach for the management of uninvestigated dyspepsia in populations with a high prevalence of H. pylori (according to the Maastricht III and IV Consensus recommendations).

Clarithromycin Resistance Mutations in Helicobacter pylori in Association with Virulence Factors and Antibiotic Susceptibility of the Strains.

Antibiotic resistance is the major cause for Helicobacter pylori eradication failure. H. pylori clarithromycin resistance mutations were evaluated in 84 (82 phenotypically clarithromycin resistant and 2 intermediately susceptible) strains by allele-specific PCR and 3'-mismatched PCR. Many (57.1%) of these strains were metronidazole resistant. Prevalence of cagA(+), cagE(+), vacA s1a, m1, i1, and i2 strains was 76.2%, 58.0%, 82.1%, 35.7%, 50.0%, and 50.0%, respectively. A2143G, A2142G, A2142C, and A2143G+A2142G mutation rates were 64.3%, 23.8%, 1.2%, and 10.7%, respectively. Strains harboring the A2142G mutation showed 5.3-fold higher clarithromycin MIC50 than those harboring the A2143G mutation. The A2143G mutation alone was 1.7-fold more common in vacA i2 strains compared with vacA i1 strains, while the A2142G mutation alone was 3-fold more frequent in vacA i1 strains than vacA i2 strains and 3.1-fold more common in metronidazole-susceptible compared with metronidazole-resistant strains. Briefly, clarithromycin resistance mutations were significantly linked to vacA i allele and metronidazole susceptibility. This is the first report about associations between the A2143G mutation and less virulent vacA i2 strains, and between the A2142G mutation and more virulent vacA i1 strains. As the 2143G mutation often predicts eradication failure by clarithromycin-based regimens, the results may be linked to the better eradication of more virulent strains compared with the less virulent strains.

Serum 8 Hydroxydeoxyguanosine and Cytotoxin Associated Gene A as Markers for Helicobacter pylori Infection.

Helicobacter pylori (H.pylori) is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomas and mucosa associated tissue lymphomas. Cytotoxin associated gene A (CagA) is one of the virulence factors of H.pylori. It is hypothesized that reactive oxygen species (ROS) play roles in H.pylori associated disease especially in development of gastric adenocarcinoma. Individuals infected with H.pylori bearing CagA produce more ROS than others. 8-hydroxydeoxyguanosine (8OHdG) is an in vitro marker of DNA damage and oxidative stress. The aim of this study was to investigate the relationship between 8OHdG level, H.pylori infection and CagA and alterations of serum 8OHdG level after H.pylori eradication. Patients admitted with dyspeptic complaints and upper gastrointestinal endoscopy were assessed. H.pylori was determined from histopathology of specimens. Serum 8OHdG levels of three groups (H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive) were compared. Patients with H.pylori infection received eradication therapy. Serum 8OHdG levels pretreatment and posttreatment were also compared. In total, 129 patients (M/F, 57/72) were enrolled in the study. Serum 8OHdG level of H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive groups were significantly different (5.77±1.35 ng/ml, 5.43±1.14 ng/ml and 7.57±1.25 ng/ml respectively, p=0.05). Furthermore, eradication therapy reduced serum 8OHdG level (6.10±1.54 ng/ml vs 5.55±1.23 ng/ml, p=0.05). Individuals infected with H.pylori bearing CagA strains have the highest serum 8OHdG level and eradication therapy decreases the serum 8OHdG level. To the best of our knowledge this is the first study that evaluated the effect of CagA virulence factor on serum 8OHdG level and the effect of eradication therapy on serum 8OHdG levels together. Eradication of CagA bearing H.pylori may prevent gastric adenocarcinoma by decreasing ROS. 8OHdG level may thus be a good marker for prevention from gastric adenocarcinoma.

STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer.

BackgroundBecause to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer.MethodsWe included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model.ResultsThe rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes.ConclusionsOur study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined.

A Meta-Analysis of the Association between Helicobacter pylori Infection and Risk of Coronary Heart Disease from Published Prospective Studies.

The association between helicobacter pylori (Hp) infection and coronary heart disease (CHD) has long been debated, and the results from previous meta-analysis are varied. The aim for this study was to identify the association between Hp and CHD using published perspective cohort studies. A systematic review and meta-analysis were performed on studies published from January, 1992 to April, 2014. All studies included used data from prospective cohort studies of CHD events or CHD deaths. Random effect models were applied in all estimations. H. pylori infection increased the risk of CHD events by 11% (19 studies, n = 22,207, risk ratio (RR) = 1.11, 95% confidence interval (CI): 1.01-1.22). This effect was greater for studies that had less than 5 years' follow-up time (RR = 1.15, 95% CI: 1.00-1.32). However, this effect was not significant for studies that had follow-up times ≥10 years (n = 5100, RR = 1.04, 95% CI: 0.87-1.24). Neither Cag-A seropositive nor Cag-A seronegative strains of H. pylori were associated with a significantly increased risk of CHD events or deaths based on the current published data. In conclusion, H. pylori infection increased the risk of CHD events, especially in a patient's early life, but this association was weaker or might be masked by other CHD risk factors in long-term observations.

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.

Duodenal ulcer promoting gene 1 (dupA1) is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

Histo-Blood Group Carbohydrates and Helicobacter pylori Infection

b , ALe b , BLe b ). Therefore, individuals carrying both FUTII and FUTIII enzymes are classified as Secretors. Non Secretors did not carry the FUTII being unable to synthesize these carbohydrate antigens but when carrying the FUTIII enzyme they express high levels of Le a an- tigen (2). These biochemical events affect the susceptibility and resist - ance to microorganisms like H. pylori. Th e experimental demonstration that the Le b glycolipd acts as an important receptor for H. pylori (3) and the subsequent characteriza- tion of its BabA adhesin (Blood group antigen binding Adhesin) (4) filled a gap opened with the old report that individuals belonging to O blood group are more prone to suffer from peptic ulcers (5). These stud - ies clearly established a functional relationship between histo-blood group carbohydrates and a microorganism infecting thousands of peo- ple around the globe. It reached its peak with the observation that H. pylori strains isolated from Amerindians are strongly adapted to infect those belonging to O blood group. This adaptability is coincident with the high prevalence of blood group O in South America natives (6). by CagA strains is strongly associated with this blood group, especially in adult patients with chronic active gastritis and peptic ulcers (9,10). Recently it was shown that the Secretor phenotype plays an im- portant role in intrinsic resistance to infection by this organism. The high concentration of mucus in carriers of this phenotype appears to be crucial in preventing the adhesion of BabA strains to histo-blood group carbohydrates expressed in the gastrointestinal tract. Addition- ally, carriers of the weak secretor phenotype (weak secretor) have par- tial protection against mucosal inflammation and proliferation of this microorganism, thus confirming the importance of the FUT2 gene in resistance to infection by some H. pylori strains (11). Although most studies show that the presence of Le b carbohydrate increase the susceptibility of O blood group for infection by H. pylori some questions concerning the contribution of histo-blood group car- bohydrates still need to be answered. Carries of chronic gastritis, peptic ulcer and gastric cancer did not present necessarily evidence of infec- tion by this microorganism. Are these carbohydrates acting only as lig- ands for H. pylori adhesion or playing additional roles in the manifesta- tion of these diseases? The gastric cancer related to H. pylori is more frequent in A blood group. What is the influence of histo-blood group carbohydrates in this differential susceptibility when compared with O blood groups? The presence of FUTII glycosyltransferase diversifies and reduces the extension of histo-blood group carbohydrate chains. What is the contribution of these short hito-blood group carbohydrate chains in infection by this organism? Understanding the biological and clinical importance of histo- blood group carbohydrates in the diseases resulting from H. pylori in- fection may provide a better basis for potential therapeutic applications. Would be possible to identify adhesins other than BabA and use them in the production of vaccines capable of inducing localized humoral immune responses with the expression of high affinity specific IgA anti- bodies. Moreover, these carbohydrates could be useful in anti-adhesion therapy which apart from deterring colonization by this microorgan- ism may contribute to the treatment of infection by strains resistant to conventional antibiotics (1). Studies aimed to clarify the relationships between histo-blood group carbohydrates and H. pylori may contribute to understanding the selective forces that created and maintain the high polymorphism of ABO, Secretor and Lewis histo-blood group carbohydrates in man.

Seroepidemiology ofHelicobacter pyloriinfection in elderly people in the Beijing region, China

To investigate seroepidemiology of cagA(+) and vacA(+) strains of Helicobacter pylori (H. pylori) in an elderly population in Beijing and to determine risk factors for seropositivity. A total of 2006 elderly persons (> 60 years) were selected using a random cluster sampling method in different parts of the Beijing area (urban, suburban and mountainous districts). Structured questionnaires were completed during home visits, including history of H. pylori infection, history of gastrointestinal diseases, diet types, hygiene habits, occupation and economic status. Blood samples (2 mL) were collected from each participant, and serum IgG antibodies to cagA, vacA and H. pylori urease antigens were measured by immunodetection. The prevalence of H. pylori infection in elderly subjects was 83.4% and the type I H. pylori strain infection rate was 56%. The seroprevalence for type I H. pylori strain infection in urban and suburban districts was higher than that in the mountainous areas (P < 0.001). Elderly subjects who had previously performed manual labor or were in the young-old age group (age < 75 years) had a higher seroprevalence of H. pylori infection than those who had previously performed mental labor or were in the oldest-old age group (age ≥ 75 year) (P < 0.05). The type I H. pylori strain infection rate in the elderly with vegetarian diets was higher than in those eating high-protein foods (P < 0.001). There was no significant difference in the prevalence of H. pylori strains between male and female elderly participants (P > 0.05). Type I H. pylori seroprevalence is higher in elderly people. The distribution of strains of H. pylori is significantly affected by age, area and dietary habits.

The relationship between Helicobacter pylori and beta-2 microglobulin in humans.

H. pylori is related to various gastrointestinal diseases. β 2 Microglobulin (β 2M) is an intrinsic element of major histocompatibility complex (MHC I). Serum β 2M level may increase in inflammatory states. The aim of current study is to evaluate the relationship between β 2M and H. pylori bearing CagA strains. Methods. H. pylori status was determined by histopathology of samples taken from stomach. CagA status and β 2M level were measured from blood samples of patients. Eradication therapy was administered to the patients with H. pylori infection. β 2 Microglobulin levels were measured before and after treatment. Results. 35 (29.2%) H. pylori(−) patients and 85 (70.8%) H. pylori (+) patients were included in the study. There were 52 (43.3%) patients with CagA negative and 33 (27.5%) patients with CagA positive H. pylori infection. The mean serum β 2M level was 1.83 mg/L in H. pylori (−) group, 1.76 mg/L in H. pylori (+) CagA (−) group, and 1.93 mg/L in H. pylori and CagA (+) group (P > 0.05). Serum β 2M levels (1.82 versus 1.64 mg/L P < 0.05) were decreased after eradication. Conclusion. H. pylori and CagA status did not affect β 2M level. Relationship between low grade systematic inflammation and H. pylori should be investigated to find out new predictors for diseases associated with inflammation.

Helicobacter pylori Seropositivities and Risk of Pancreatic Carcinoma

Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain-specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common. We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays. Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index. Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma. H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site.