Helicobacter pylori promotes gastric cancer metastasis via up-regulating the expression of Bmi-1 / 细胞与分子免疫学杂志

Objective To clarify whether Helicobacter pylori (H. pylori) can promote metastasis of gastric cancer cells via the high-expression of induced B cell specific Moloney murine leukemia virus integration site 1 (Bmi-1). Methods The gastric cancer tissue specimens from 82 patients were collected for this study. The protein and gene expression level of Bmi-1 in gastric adenocarcinoma tissue were detected by immunohistochemistry and real time quantitative PCR, respectively. And meanwhile the correlation between Bmi-1 levels and pathological features, and prognosis of gastric cancer were analyzed retrospectively. Then, the GES-1 cells were transfected with pLPCX-Bmi-1 plasmid and infected with H. pylori respectively. After the Bmi-1 overexpression in GES-1 cells, the invasion ability of the GES-1 cells was detected by Transwell assay, and the cell cycle and apoptosis were detected by flow cytometry. Results The mRNA and protein of Bmi-1 expression in gastric cancer tissues were higher than tumor-adjacent tissue, and the high expression of Bmi-1 was positively correlated with tumor invasion, TNM stage, tumor differentiation, lymph node metastasis and H. pylori infection. When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection, the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively. Conclusion H. pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.

Increased expression of interleukin-6 gene in gastritis and gastric cancer

Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Nucleotide Binding Oligomerization Domain 1 Is an Essential Signal Transducer in Human Epithelial Cells Infected with Helicobacter pylori That Induces the Transepithelial Migration of Neutrophils

BACKGROUND/AIMS: The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner. METHODS: Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor kappaB (NF-kappaB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified. RESULTS: Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls. CONCLUSIONS: Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-kappaB activation and IL-8 expression in H. pylori-infected human epithelial cells.

Genetic Susceptibility of Gastroduodenal Disease in Ethnic and Regional Diversity

No abstract available.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Comparación de Helicobacter pylori en cavidad oral y mucosa gástrica de acuerdo a genotipo de virulencia (cagA y vacAm 1) / Comparison of Helicobacter pylori in oral cavity and gastric mucosa according to virulence genotype (cagA and vacA m 1)

Objective: To compare the virulence genotype (cagA and vacA ml genes) of Helicobacter pylori obtained simultaneously from gastric mucosa and oral cavity. Material and Methods: Gastric samples of 18 patients were obtained by endoscopic biopsies. Oral samples of these patients were obtained from dental plaque and saliva swabs from the floor of the mouth and the base of the tongue. All samples were studied by conventional PCR and real-time PCR (RT-PCR). Virulence genes cagA and vacA ml were studied by RT- PCR. Results: According to presence and/or absence of cagA and vacAm1 genes, seven different combinations were observed. Conclusion: These results suggest that there is a variety of genetic profiles of Helicobacter pylori in the stomach and oral cavity, with a predominance of less virulent genotypes in the patients included in this study (cagA-, vacA m1-).

Objetivo: Comparar el genotipo de virulencia (genes cagA y vacA m1) de Helicobacter pylori, obtenido simultáneamente de mucosa gástrica y cavidad oral. Material y Métodos: Para esto se incluyeron muestras de biopsias gástricas de 18 pacientes. Las muestras orales de estos pacientes fueron obtenidas de placa bacteriana y saliva del piso de boca y base de la lengua. Las muestras fueron estudiadas con RPC convencional y RPC en tiempo real (RPC-TR). Los genes de virulencia cagA y vacA m1 fueron estudiados con RPC-TR. Resultados: De acuerdo a la presencia o ausencia de los genes de virulencia cagA y vacA m1 detectados en las muestras gástricas y orales, se pudieron diferenciar siete combinaciones diferentes. Conclusión: Estos resultados sugieren que existe una variedad de genotipos de virulencia en Helicobacter pylori en el estómago y la cavidad oral, predominando en los pacientes incluidos en este estudio las cepas con genotipos asociados a menor virulencia (cagA-, vacA m1-).

Asociación de los polimorfismos IL-1B-511 e IL-1RN y Helicobacter pylori CagA positivo con cáncer gástrico en una zona de riesgo alto en Colombia / Association of interleukin-1 genetic polymorphism and CagA positive Helicobacter pylori with gastric cancer in Colombia

Background: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. Aim: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. Material and Methods: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. Results: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95 percent confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95 percentCI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95 percentCI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95 percentCI 0.01-0.65). Conclusions: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.

Virulence attributes of Helicobacter pylori isolates & their association with gastroduodenal disease.

Background & objectives Certain genotype(s) of Helicobacter pylori strains may play important role in the development of gastric cancer (GC) and peptic ulcer disease (PUD). This study was undertaken to investigate the association of cagA, cagA3/ region subtypes, babA2 and vacA genotypes of H. pylori with GC, PUD and non-ulcer dyspepsia (NUD) as there are no such studies from India. Methods A total of 348 consecutive adult patients (NUD 241, PUD 45, GC 62) undergoing upper gastrointestinal endoscopy between September 2002 and May 2007 in a tertiary referral centre at Lucknow, north India, were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Genotyping for cagA, cagA3/ subtypes, babA2 and vacA was performed by PCR using sequence specific primers. Results H. pylori infection was higher in patients with PUD than with GC (80 vs. 56.5%, P < 0.01) and NUD (80 vs. 55.2%, P= 0.002). cagA positive H. pylori isolates were detected in 80 per cent in GC, 83.3 per cent in PUD and 76.7 per cent in NUD with no significant difference among them. Only A subtype of cagA3/ was detected and its distribution in GC, PUD and NUD was 68.8, 69.4 and 52.6 per cent respectively. Presence of babA2 genotype was 31.4 per cent and it had significant association with PUD when compared with NUD (52.8 vs. 26.3%, P<0.003). On univariate regression analysis, s1a allele was associated with GC (P<0.050) and s1a/m2 vacA genotype with both GC (P=0.014) and PUD (P=0.016). Interpretation & conclusions H. pylori infection was strongly associated with PUD with a very high proportion of patients with GC have s1a allele and s1a/m2 vacA genotype. Both s1a/m2 vacA genotype and babA2 are associated with PUD. The study shows that different virulence attributes of H. pylori are involved in different gastroduodenal disorders.

ABO blood groups and Helicobacter pylori cagA infection: evidence of an association

Diseases resulting from Helicobacter pylori infection appear to be dependent on a host of genetic traits and virulence factors possessed by this microorganism. This paper aimed to investigate the association between the ABO histo-blood groups and H. pylori cagA infections. Genomic DNA samples (n = 110) of gastric biopsies obtained from patients with endoscopic diagnosis of peptic ulcers (n = 25) and chronic active gastritis (n = 85) were analyzed by PCR using specific primers for the cagA gene. Of the samples, 66.4 percent (n = 73) tested positive and 33.6 percent (n = 37) negative for the gene. The cagA strain was predominant in peptic ulcers (n = 21; 84.0 percent) compared with chronic active gastritis (n = 52; 61.2 percent) (p = 0.05; OR 3.332; 95 percent CI: 1.050-10.576). Additionally, the cagA strain was prevalent in the type O blood (48/63; 76.2 percent) compared with other ABO phenotypes (25/47; 53.2 percent) (p = 0.01; OR 2.816; 95 percent CI: 1.246-6.364). These results suggest that H. pylori cagA infection is associated with the O blood group in Brazilian patients suffering from chronic active gastritis and peptic ulcers.

Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians.

Background & objectives: Genetic polymorphism of CYP2C19 is known to occur with a frequency of 12 per cent in north Indian population. But no study correlated CYP2C19 genetic polymorphism with eradication of Helicobacter pylori in north Indian gastritis patients positive for H. pylori and hence this study. Methods: Ninety one consecutive patients positive for H. pylori fulfilling the study criteria were phenotyped and genotyped for CYP2C19. They were given 20 mg omeprazole (OPZ), 750 mg amoxicillin (AMC) and 500 mg tinidazole (TNZ) (bid) for 7 days followed by 20 mg OPZ (qd) for 21 days. Non eradicated extensive metabolizers (EMs) were retreated with 40 mg OPZ (bid) and 500 mg AMC (qid) for 14 days. Results: EMs and poor metabolizers (PMs) excreted 4.26 ± 0.34 (95% CI 3.59-4.92) and 0.73 ± 0.05 (95% CI 0.63-0.82) μmol 5-OH-OPZ in 8 h, respectively. After initial therapy, EMs demonstrated 37 per cent (95% CI: 24.5-49.5) and PMs 92 per cent (95% CI: 77-107) eradication of H. pylori. Non eradicated EMs after retreatment demonstrated 90 per cent (95% CI: 79-101) eradication. Interpretation & conclusions: This study demonstrated a direct correlation between CYP2C19 genetic polymorphism and H. pylori eradication in north Indian patients with gastritis. Knowing the CYP2C19 phenotype of a patient may help in prescribing optimum dose of proton pump inhibitor to achieve better therapeutic outcome.

Association of Helicobacter pylori restriction endonuclease-replacing gene, hrgA with overt gastrointestinal diseases / Associação entre o hrgA (Helicobacter pylori restriction endonuclease-replacing gene) com as principais doença gastrointestinais

BACKGROUND and AIM: Helicobacter pylori has been proven to be responsible for causing various gastrointestinal disorders including gastric adenocarcinoma. Several genes of pathogen (the genes of the cag-PAI, vacA, iceA, and babA) either in combination or independently have been reported to significantly increase the risk of ulceration/gastric carcinoma, with the cagA gene having the strongest predictive value. Pursuit to identify new genes which could serve as a marker of overt disease progression, lead to the discovery of hrgA gene. METHODS: Fifty-six indigenous strains of H. pylori from subjects with various gastric disorder were screened to assess the status of hrgA gene along with the cagA gene using simple polymerase chain reaction using specific oligonucleotide primers. Post-amplification, amplicons were subjected for sequencing to identify any strain specific variations in sequences from the H. pylori isolated from different disease manifestations. Histopathological analysis was done to ascertain any significant change in the histological scores of subjects infected with cagA+/hrgA+ and cagA-/hrg+ strains. RESULTS: All the 56 (100 percent) subjects amplified with the oligonucleotide primers specific to hrgA gene, whereas 81.71 percent subjects showed the presence of cagA gene. Sequencing of the amplimers showed 99 percent homology. Histology of the cagA+/hrgA+ and cagA-/hrg+ subjects did not show any significant difference. CONCLUSION: hrgA gene of Helicobacter pylori is not a ideal surrogate marker for identifying individuals with higher risk of developing overt gastro-duodenal diseases such as neoplasia of the stomach.

RACIONAL e OBJETIVOS: O Helicobacter pylori tem sido incriminado como causador de vários distúrbios digestivos, incluindo o adenocarcinoma gástrico. Diversos genes patogênicos (os genes do cag-PAI, vacA, iceA e babA), em combinação ou independentes, têm sido reportados como fatores de aumento de risco para ulceração/carcinoma gástrico, tendo o gene cagA forte valor preditivo. A procura da identificação de novos genes que possam vir a ser marcadores da progressão da doença levaram à descoberta do gene hrgA. MÉTODOS: Cinqüenta e seis amostras de H. pylori provenientes de pacientes com diversas afecções gástricas foram examinadas para caracterizar a presença do hrgA juntamente ao cagA, usando iniciadores específicos da reação de cadeia da polimerase. Após amplificação, os produtos amplificados pela PCR foram seqüenciados para a identificação de variações específicas nas seqüências do H. pylori isolado de diferentes doenças gastroduodenais. A análise histopatológica foi feita para assegurar qualquer mudança significativa nos escores dos indivíduos infectados com cagA+hrgA+ e cagA-/hrgA+. RESULTADOS: Todas as 56 amostras (100 por cento) foram amplificadas com iniciadores específicos para o hrgA, enquanto que 81,71 por cento mostraram a presença do cagA. O seqüenciamento do produto amplificado pela PCR mostrou 99 por cento de homologia. A histologia entre os grupos cagA+/hrgA+ e cagA-/hrgA+ não mostrou nenhuma diferença significante. CONCLUSÃO: O gene hrgA do H. pylori não é o marcador ideal para identificar indivíduos com alto risco de desenvolvimento de doenças gastrointestinais como a neoplasia de estômago.

Detección de Helicobacter pylori en mucosa gástrica y cavidad oral / Helicobacter pylori detection in gastric and oral mucosa

Helicobacter pylori (H pylori) infection has been related to various gastroduodenal disorders. The objective of this study was to detect H pylori in gastric mucosa and relate it to its presence in the oral cavity. Fifty-four patients with medical indication oi digestive endoscopy from the Gastroenterology Unit of the Regional Hospital of Concepción, Chile, were studied. Gastric samples were obtained from each patient from antrum and corpus through endoscopic biopsies. Oral samples were obtained from dental plaque and saliva swabs from the floor of the mouth and the base of the tongue. Oral and gastric sample were studied by culture. Oral samples from patients with positive gastric cultures for H pylori (n = 21) were studied by culture, conventional PCR and Real Time PCR. Ail cultures from oral samples were negative (0/21) for H pylori. Only one sample of dental plaque was positive with conventional PCR (1/21), while ail samples of saliva were negative. However, samples from ail patients were positive with Real Time PCR (20/21 dental plaque, 21/21 saliva from the floor of the mouth, 20/21 saliva from the base of the tongue). The results suggest that there is a correlation between the presence of H pylori in gastric mucosa and the oral cavity. Also, that Real Time PCR the best technique to detect low number of bacteria in the oral cavity.

La infección por Helicobacter pylori está vinculada a diversas patologías gastroduo-denales. El objetivo de este estudio fue detectar H. pylori en la mucosa gástrica y relacionar su presencia con H. pylori en la cavidad oral. Se estudiaron 54 pacientes de la Unidad de Gastroenterología del Hospital Regional de Concepción, con indicación de endoscopía digestiva alta. Para cada paciente se realizó biopsia de mucosa gástrica (antro y cuerpo), y se obtuvieron 3 muestras orales (placa bacteriana, saliva de la base de la lengua y piso de boca). Las muestras gástricas y orales fueron cultivadas. Las muestras orales de los pacientes que presentaron cultivos de biopsia gástrica positivos para H. pylori (n = 21) fueron sometidas a análisis de detección de la bacteria mediante cultivo, PCR convencional y PCR de Tiempo Real. Los resultados obtenidos para las muestras orales fueron: cultivo 100 por ciento negativos (0/21), con PCR convencional se detectó H. pylori sólo en un paciente (una muestra de las 3 en placa bacteriana) (1/21), mientras que todas las muestras de saliva de piso de boca y base de la lengua fueron negativas. Veintiún pacientes resultaron positivos para la bacteria por la técnica de PCR de Tiempo Real en las muestras orales, 20/21 en muestras de placa bacteriana, 21/21 en saliva de piso de boca y 20/21 en base de lengua. Los resultados sugieren que existe correlación entre la presencia de H. pylori en la mucosa gástrica y en la cavidad oral. Además, que la técnica de PCR de Tiempo Real es la más adecuada para detectar el bajo número de bacterias de H. pylori de la cavidad oral.

Helicobacter pylori infection and hyperemesis gravidarum: possible causal relationship with evaluation of a new immunoassay in stool compared with standard diagnostic techniques

The aim of the present study was to investigate any possible association between infection with Helicobacter pylori [H. pylori] and hyperemesis gravidarum [HG]. Moreover; evaluation of different methods used in the diagnosis of H. pylori during pregnancy aiming to present a simple non-invasive and reliable method. 68 pregnant women with hyperemesis gravidarum and 72 control pregnant women were enrolled in the study. All participants were examined both for H. pylori serum immunoglobulin G antibodies [HpIgG Ab], showing chronic infection, and H. pylori stool antigens [HpSA], and showing active gastrointestinal colonization. Serologically positive H. pylori infection was detected in 59 [86.8%] subjects of the hyperemesis gravidarum group and in 32 [44.4%] of the controls [P<0.01]. HpSA was detected in 45.6% of patients with hyperemesis gravidarum, whereas only 5.6% of patients in the control group were positive for this specific antigen [P<0.001]. The new stool immunoassay test had a sensitivity of 96% [95% confidence interval 90.6% to 100%], specificity of 93% [85.1% to 99.5%], positive predictive value of 92%, and negative predictive value of 96%. In conclusion, this study supports the studies suggesting an association between H. pylori and HG. Infection with H. pylori should be kept in mind in cases of HG in pregnant women. The findings of the current study have, also, demonstrated that HpSA as a relatively simple, inexpensive and time saving noninvasive test is a reliable method for detection of active H. pylori infections in pregnant women with hyperemesis gravidarum. This stool immunoassay represents a new, accurate, and non-invasive method for H pylori infection that overcomes the limitations of existing tests

Analysis of Helicobacter pylori antimicrobial susceptibility and virulence genes in gastric mucosal biopsies in the United Arab Emirates.

AIM: To determine the virulence attributes (presence of cagA and vacA genes) of Helicobacter pylori , and presence of clarithromycin resistance genes in gastric mucosal biopsy samples obtained in the United Arab Emirates. METHODS: DNA was extracted from antral gastric biopsy samples from 91 dyspeptic patients. Real-time PCR and melting curve analysis were used to identify patients infected with H. pylori and to further identify strains containing the A(2142/43)G or the A(2142)C mutations that are associated with clarithromycin resistance. PCR was also used to identify cagA - and vacA -positive strains. RESULTS: Real-time PCR analysis detected the presence of H. pylori in 55 (60%) samples. Thirty-six pathogen-positive samples contained at least one of three point mutations associated with clarithromycin resistance. The vacA gene was present in 40 (72.7%) and cagA was present in 41 (74.5%) of the positive samples. Both genes were present in 36 (65%) of the positive samples. The presence of each clarithromycin-inducing mutation was largely independent of the others. Mutation at one position, A(2142/43)G, was strongly associated with the presence of both the vacA gene and the cagA gene. CONCLUSIONS: A high proportion of gastric mucosal biopsies obtained in the UAE is positive for genes associated with clarithromycin resistance. This may have implications for treatment of the infection.

Helicobacter pylori cagA, vacA and iceA genotypes in northern Thai patients with gastric disease.

Helicobacterpylori, a common infectious bacterium, has been linked to chronic gastritis, peptic ulcer and gastric cancer. Gastric biopsy specimens were obtained from 58 northern Thai patients with gastritis, 28 with gastric ulcer, 45 with duodenal ulcer and 4 with gastric cancer. cagA, vacA s1 and iceA gene was found in 88, 98, and 89% of the specimens, respectively. For vacA, the frequency of subtype s1a, s1c and combined sla and s1c was 40, 16, and 41%, respectively. The frequency of subtype s1a/m1 and s1a/s1c/m1 was 27 and 20%, respectively. Fifty-three patients (39%) were infected with multiple vacA genotypes but there was no association with clinical outcome. cagA positive and mixed vacA s1a and s1c strains were found in significantly more cases of duodenal ulcer than gastritis (p < 0.05). For iceA, subtype iceA1 reached a frequency of 60%, whereas subtype iceA2 was only 24%.

Microsatellite Instability in Gastric B-cell Lymphoma / 대한소화기학회지

BACKGROUND/AIMS: Microsatellite instability (MSI) reflects the defect in DNA mismatch repair (MMR) pathways and plays an important role in certain malignancies. However, the role of MSI in the development of gastric B-cell lymphomas remains unsettled. We aimed to investigate the clinical significance of MSI in patients with gastric B-cell lymphoma. METHODS: Seven micosatellite loci (BAT25, BAT26, D2S123, D5S346, D17S250, D14S50, IGF-IIR) were used for MSI analyses. Microsatellite genotypes were categorized as microsatellite stable (MSS, no positive marker), low frequency MSI (MSI-L, 40% positive marker). Among the gastric B-cell lymphoma patients who underwent MSI analysis between September 2002 and May 2003, twenty-two patients were enrolled. Median follow-up duration was 23 months (6-32 months). RESULTS: Median age was 46 years (26-73 years). Male to female ratio was 1:1.4. Twelve patients (54.5%) underwent Helicobacter pylori (H. pylori) eradication and ten patients (45.5%) underwent chemoradiation therapy. No case presented MSI-H. MSI-L was observed in 40.9% (9/22). Between MSS group and MSI-L group, there was no significant difference in age, tumor stage, location, grade of large cell component, H. pylori infection, bulk of tumor and proportion of regression or recurrence. All positive markers belonged to the dinucleotide markers. CONCLUSIONS: The current study suggests that the role of MSI is questionable in the development of gastric B-cell lymphoma due to their low incidence.

Relación de la genotipificación de Helicobacter pylori con la forma e intensidad de la gastritis en población adulta portadora de patología gástrica benigna / Association between helicobacter pylori genotype and the severity of gastritis in infected adults

Background: The damaging capacity of Helicobacter pylori is variable and depends, in part, on its genetic polymorphism. Aim: To study H pylori genes vacA, cagA and iceA and the relationship of these genotypes with the features of acute damage in chronic gastritis. Material and methods: Gastric endoscopic biopsies were obtained in 75 adults for pathological study and genetic typification of H pylori by specific PCR. Results: In only 64 cases, complete information was available. In 53 of these, there was H pylori infection demonstrated by PCR. Twenty one percent had infection by two or more H pylori strains, vacA gene had genotypes s2/m2, s1/m1 and s1/m2 in 36, 25 and 8% of cases respectively, cagA gene was present in 49% of infected patients. iceA gene had genotypes iceA 1 ad iceA 2 in 15 and 60% of patients respectively. The presence of cagA or alleles s1/m1 and s1/m2 of vacA gene was directly correlated with polymorphonuclear infiltration and the severity of epithelial damage. The genotype s2/m2 of vacA gene was significantly associated with a milder or absent mucosal damage. No association was found between iceA alleles and the pathological features of gastritis. Conclusions: Alleles of vacA and cagA genes of H pilory are associated with the severity of gastric mucosal damage.

Prevalência de Helicobacter pylori no interior do Rio Grande do Sul / Prevalence of Helicobacter pylori in a town located in the State of Rio Grande do Sul, Brazil

Em estudo retrospectivo, transversal, realizado em Passo Fundo, cidade localizada no interior do Rio Grande do Sul, analisaram-se 1.469 exames de endoscopia digestiva alta consecutivos, com biópsias para anatomopatológicos. Verificou-se que a maior prevalência de indivíduos com Helicobacter pylori ocorre na quinta década de vida. A região apresenta prevalência de 49,48 por cento , sendo de 51,36 por cento a da infecção nas mulheres e de 46,67 por cento nos homens. O impacto desse agente infeccioso justifica esforços no sentido de identificar medidas preventivas

Relevance of vacA Genotypes of Helicobacter pylori to cagA Status and Its Clinical Outcome

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 ; 76.9% versus 62.3% or 64.9%, res pectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.