In Peripheral Blood Mononuclear Cells Helicobacter pylori Induces the Secretion of Soluble and Exosomal Cytokines Related to Carcinogenesis.

Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1ß, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein-protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.

Filogeografía de glmM en cepas de Helicobacter pylori aisladas de pacientes con patologías gástricas al sur de México / Phylogeography of glmM in Helicobacter pylori strains isolated from patients with gastric pathologies in southern Mexico

INTRODUCCIÓN: Helicobacter pylori posee un genoma de aproximadamente 1600 genes, el gen glmM está altamente conservado y se ha utilizado para identificar H. pylori por su sensibilidad y especificidad en biopsias gástricas. La diversidad genética de H. pylori es alta entre cepas del mismo origen geográfico y es aún más a escala global. En México, son pocos los estudios que destacan la importancia de la variabilidad genética de esta bacteria, la cual es estudiada mediante técnicas moleculares. OBJETIVO: Analizar la variabilidad genética del gen glmM en cepas de H pylori de pacientes con patologías gástricas. METODOLOGÍA: Se analizaron solo 90 secuencias del gen glmM (10 de grupo de estudio y 80 depositadas en el GenBank), posteriormente realizamos redes de haplotipos, donde se puede observar las diferencias en pasos mutacionales de las secuencias a nivel estatal y con otros grupos geográficos con el fin de hacer una reconstrucción de filogenia basada en las relaciones ancestro-descendiente. RESULTADOS: Las cepas analizadas provenían el 30% hombres y 70% mujeres, con una edad promedio de 42 años, con diagnóstico de gastritis, las secuencias de glmM mostraron variabilidad genética. De las secuencias analizadas, se propone confirmar la presencia de ocho haplotipos que se agrupan separados. CONCLUSIONES: Se sugiere hacer estudios detallados a nivel molecular de los haplotipos del gen glmM en cepas de H. pylori para conocer su distribución geográfica con la finalidad de conocer las cepas circulantes a nivel mundial y con esto evitar los resultados negativos

INTRODUCTION: Helicobacter pylori has a genome of approximately 1600 genes, the glmM gene is highly conserved and has been identified to identify H. pylori due to its sensitivity and specificity in gastric biopsies. The genetic diversity of H. pylori is high among strains of the same geographical origin and is even more of a global scale. In Mexico, studies that study the importance of the genetic variability of this bacterium, which is studied by molecular techniques. AIM: To analyze the genetic variability of the glmM genus in H pylori strains of patients with gastric pathologies. METHODOLOGY: Only 90 sequences of the glmM genus were analyzed (10 of study group and 80 deposit in GenBank), to carry out haplotype networks, where the differences in the steps of the relationships at the state level and with other geographical groups can be observed in order to do a reconstruction of phylogeny based on ancestor-descendant relationships. RESULTS: The strains analyzed showed 30% of men and 70% of women, with an average age of 42 years, diagnosed with gastritis, the glmM sequences. From the sequences analyzed, it is proposed to confirm the presence of eight haplotypes that are grouped separately. CONCLUSIONS: We suggest university studies at the molecular level of the glmM haplotypes in strains of H. pylori to know their geographical distribution in order to know the circulating strains worldwide and with this avoid negative results

CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

BACKGROUND: Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans. One of the main virulence factors of H. pylori is the cag pathogenicity island (cagPAI), which encodes a type 4-secretion system (T4SS) and the cytotoxin CagA. Translocation of CagA through the T4SS triggers host-signaling pathways. One of the T4SS proteins is CagL, which is necessary for CagA translocation. CagL is a 26-kDa protein that contains a hypervariable motif, which spans residues 58 to 62. Several polymorphisms in this region have been associated with different disease outcomes, e.g. in Mexico, N58 is associated with a higher risk of gastric cancer. The aim of this work is to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the vacA genotype. RESULTS: Of the 164 biopsies analyzed, only 30.5% (50/164) were positive for H. pylori. Thirty-six of the 50 clinical isolates (72%) were cagA positive, and 40 (80%) had the most virulent vacA genotype (s1/m1). Of the cagA positive strains, 94.4% were vacA s1/m1. All the cagA + strains contained the cagL gene. The most prevalent sequence in the polymorphic region (residues 58-62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33), and DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33). Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33). Only two isolates (6.1%) contained residues N58/E59, which correspond to those found in H. pylori strain ATCC 26695. 92.6% of the clinical isolates having polymorphism D58/K59 had the genotype vacA s1/m1, considered to be the most virulent, while 7.4% had the genotypes vacA s1/m2 and s2/m2. CONCLUSIONS: In Mexican patients, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are more common in patients with chronic gastritis.

Multiple infections by EBV, HCMV and Helicobacter pylori are highly frequent in patients with chronic gastritis and gastric cancer from Southwest Mexico: An observational study.

The chronic inflammation and damage to the gastric epithelium induced by Helicobacter pylori (H. pylori) are the main risk factors for gastric cancer development. Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) induce chronic inflammation and have been found in gastric tumors. The objectives this observational study were to determine the frequency of multiple infections by Helicobacter pylori, Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) and to relate the infection by EBV and HCMV with H. pylori vacA/cagA genotypes in patients with chronic gastritis or gastric cancer. DNA from H. pylori, EBV and HCMV was detected by PCR in biopsies from 106 Mexican patients with chronic gastritis and 32 from gastric cancer. The cagA status and the vacA genotypes of H. pylori were determined by PCR. In chronic gastritis and gastric cancer EBV was found in 69.8% and 87.5%, HCMV in 52.8% and 53.1%, and H. pylori in 48.1% and 40.6%, respectively. In chronic gastritis, 53% of H. pylori patients were EBV and 33% were both EBV/HCMV; in gastric cancer, 92.3% of H. pylori-infected individuals were EBV and 46.1% were EVB/HCMV. All the intestinal- and mixed-type tumors and the 83.3% of diffuse-type tumors were EBV. No significant differences were found between single infections or coinfections with the diagnosis or the cancer type. The H. pylori genotypes were not related to EBV or HCMV infection. The frequency of dual infections by H. pylori, EBV and HCMV is higher in patients from southwest Mexico than other populations. It is likely that these pathogens act synergistically to induce inflammation and gastric cancer.

vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

PURPOSE: Virulent genotypes of Helicobacter pylori vacA s1m1/cagA+/babA2+ have been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic proteins, and their association with the disease is allele-dependent. The aims of this work were: (i) to determine the prevalence of H. pylori by type of chronic gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in strains from patients with different types of chronic gastritis; (iii) to characterize the variable region of cagA alleles. METHODOLOGY: A total of 164 patients with chronic gastritis were studied. Altogether, 50 H. pylori strains were isolated, and the status of cagA, babA2 and vacA genotypes was examined by PCR. cagA EPIYA segment identification was performed using PCR and sequencing of cagA fragments of six randomly selected strains.Results/Key findings. The overall prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the strains, respectively. The most frequent genotypes were vacA s1m1/cagA+/babA2- and vacA s1m1/cagA+/babA2+, with 40 % (20/50) and 28 % (14/50), respectively. In cagA+, the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in 66.6 % of the sequenced strains. CONCLUSION: H. pylori strains carrying vacA s1m1, cagA+ and babA2- genotypes were the most prevalent in patients with chronic gastritis from the south of Mexico. In the cagA+ strains, the EPIYA-ABC motif was the most common.

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.

Clarithromycin resistance and prevalence of Helicobacter pylori virulent genotypes in patients from Southern México with chronic gastritis.

In developing countries, clarithromycin resistance and frequency of re-infection are factors that contribute to high prevalence of Helicobacter pylori infection. The aim of this research was determine the prevalence of clarithromycin resistance and its relation with A2142G, A2142C and A2143G mutations in the domain V of the 23S rRNA gene of H. pylori isolates in patients from Southern Mexico with chronic gastritis. Another purpose of this work was to study the prevalence of virulent genotypes and distribution of resistant strains according to the vacA/cagA/babA2 H. pylori genotypes. One hundred forty-four patients with chronic gastritis were studied. Forty-five H. pylori strains were isolated and clarithromycin susceptibility was determined by the disk-diffusion method. The 82.2% of the strains had the combination of alleles vacA s1 m1 and the cagA gene was detected in 77.8% and 40% of the strains were babA2 positive. The vacA s1 m1 genotype was detected more frequently in cagA(+) strains, vacA s1m1/cagA(+)/babA2(-) genotype was more frequent than vacA s1m1/cagA(+)/babA2(+), 37.8% and 33.3%, respectively. Eight strains were clarithromycin resistant, in three of these, point mutations were identified, but only in one strain the A2143G mutation associated with clarithromycin resistance was found. Other point mutations (A1821G, G1826A, T1830C, A2089G, T1600C, C1601T, C1602T, T1610C, A1611C and T1633G) that have not been associated with clarithromycin resistance were identified. The highest proportion of resistant strains was vacA s1m1/cagA(+) (62.5%). In patients from southern Mexico with chronic gastritis, the prevalence of clarithromycin resistance is within internationally accepted range (17.8%) and allows continued use of triple therapy for H. pylori eradication. However, it is necessary to monitor the evolution of clarithromycin resistance in this area. The largest proportion of resistant H. pylori strains is not harboring the A2142G, A2142C and A2143G mutations in the 23S rRNA gene (87.5%). The vacA s1m1/cagA(+) genotype was the most prevalent and among clarithromycin-resistant strains, this was the predominant.

The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population.

BACKGROUND: Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer. METHODS: A total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3' variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer. RESULTS: H. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3-15.1; p < 0.001) and gastric cancer (OR = 5.9, 95% CI = 1.5-22.1) were significantly increased in individuals who harbored the EPIYA-ABCC cagA gene pattern. CONCLUSIONS: cagA-positive H. pylori is highly prevalent in southern Mexico, and all CagA variants were of the western type. The cagA alleles that code for EPIYA-ABCC motif patterns are associated with peptic ulcers and gastric cancer.

vacA genotypes of Helicobacter pylori in the oral cavity and stomach of patients with chronic gastritis and gastric ulcer

Introduction Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy. Materials and methods A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping. Result sIn 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were salivanegative/biopsypositive and 6.6% (13/196) were salivapositive/biopsynegative. In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients salivapositive/biopsypositive two genotypes were found in saliva, and one or both in the stomach. Conclusions The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector (AU)

Introduccion Helicobacter pylori (H. pylori) se adhiere a diversos componentes de la saliva humana, por ello, el objetivo de esta investigación fue detectar H. pylori en saliva y biopsia gástrica y determinar la concordancia entre los genotipos vacA encontrados en saliva y estómago del mismo paciente. Material y métodos Se estudiaron 162 pacientes con gastritis crónica y 34 con úlcera gástrica. De cada paciente se obtuvo una muestra de saliva y biopsia gástrica. El ADN de H. pylori se detectó por PCR convencional y la genotipificación de vacA se hizo por PCR anidada. Resultados En el 24% (47/196) de los pacientes se encontró ADN de H. pylori en saliva y biopsia; el 52,5% (103/196) fueron salivanegativos/biopsiapositivos y el 6,6% (13/196) resultaron salivapositivos/biopsianegativos. En 41,5% de los pacientes con gastritis crónica, se encontró H. pylori vacA s1m1, s1m2 o ambos en saliva. El 47,2% tenían>1 genotipo y en 36% de esos se encontró la combinación s1m1/s1m2. H. pylori vacA s1m1 y s1m2 también se encontró en saliva y biopsia de pacientes con úlcera. El acuerdo entre los genotipos encontrados en saliva y biopsia de los mismos pacientes fue del 51,1%. En el 27,6% de los 47 pacientes salivapositivos/biopsiapositivos se encontraron 2 genotipos en saliva, y uno o los 2 también se encontraron en estómago. Conclusiones Los genotipos s1m1/s1m2 solos o coexistiendo se encuentran simultáneamente en saliva y biopsia de los mismos pacientes. Los resultados sugieren que H. pylori alcanza la cavidad oral por diversas vías y la saliva puede servir de vehículo para la transmisión y reinfección (AU)

vacA genotypes of Helicobacter pylori in the oral cavity and stomach of patients with chronic gastritis and gastric ulcer.

INTRODUCTION: Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy. MATERIALS AND METHODS: A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping. RESULTS: In 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were saliva(negative)/biopsy(positive) and 6.6% (13/196) were saliva(positive)/biopsy(negative). In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients saliva(positive)/biopsy(positive) two genotypes were found in saliva, and one or both in the stomach. CONCLUSIONS: The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector.

vacA genotypes in oral cavity and Helicobacter pylori seropositivityamong adults without dyspepsia

Objective: The aims of this research were to determine the prevalence of Helicobacter pylori and its vacA genotypesin oral cavity in persons without dyspepsia and to establish the association between the presence of H. pylori in oralcavity and oral hygiene. The seroprevalence of anti-H. pylori antibodies and its associated factors were analyzed too.Study design: For the study, 200 adults without dyspepsia symptoms were selected. Dental plaque and salivasamples from each subject were obtained. H. pylori detection in oral samples was carried out by polymerase chainreaction (PCR) and for vacA genotyping a semi-nested and nested PCR was used. The enzyme-linked immunosorbentassay (ELISA) was used to detect anti-H. pylori IgG and IgM. The data were analyzed with Chi squareand Fisher exact test and the statistical significance was set to 0.05.Results: Of 200 subjects tested, 124 (62%) were seropositive. H. pylori was detected in the oral cavity of 34subjects (17%) and vacA allelotypes were typified in 12 of those samples. The s1 allele was detected in 8 (66.7%)samples and in one of them m1 and m2 alleles were found. In four subjects vacA m1 subtypes were found and intwo of those both m1 and m2 alleles were detected. The prevalence of H. pylori in oral cavity was higher (l8.5%)among seropositive subjects compared with seronegative persons. No association was found between the presenceof H. pylori and oral hygiene habits.Conclusions: The presence of H. pylori in oral cavity is more frequent in seropositive subjects without dyspepsiasymptoms and could represent the source of gastric infection and bacterial transmission. The data suggest thatmore than one H. pylori strain may exist in the mouth of asymptomatic persons (AU)

vacA genotypes in oral cavity and Helicobacter pylori seropositivity among adults without dyspepsia.

OBJECTIVE: The aims of this research were to determine the prevalence of Helicobacter pylori and its vacA genotypes in oral cavity in persons without dyspepsia and to establish the association between the presence of H. pylori in oral cavity and oral hygiene. The seroprevalence of anti-H. pylori antibodies and its associated factors were analyzed too. STUDY DESIGN: For the study, 200 adults without dyspepsia symptoms were selected. Dental plaque and saliva samples from each subject were obtained. H. pylori detection in oral samples was carried out by polymerase chain reaction (PCR) and for vacA genotyping a semi-nested and nested PCR was used. The enzyme-linked immunosorbent assay (ELISA) was used to detect anti-H. pylori IgG and IgM. The data were analyzed with Chi square and Fisher exact test and the statistical significance was set to 0.05. RESULTS: Of 200 subjects tested, 124 (62%) were seropositive. H. pylori was detected in the oral cavity of 34 subjects (17%) and vacA allelotypes were typified in 12 of those samples. The s1 allele was detected in 8 (66.7%) samples and in one of them m1 y m2 alleles were found. In four subjects vacA m1 subtypes were found and in two of those both m1 and m2 alleles were detected. The prevalence of H. pylori in oral cavity was higher (18.5%) among seropositive subjects compared with seronegative persons. No association was found between the presence of H. pylori and oral hygiene habits. CONCLUSIONS: The presence of H. pylori in oral cavity is more frequent in seropositive subjects without dyspepsia symptoms and could represent the source of gastric infection and bacterial transmission. The data suggest that more than one H. pylori strain may exist in the mouth of asymptomatic persons.

Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis.

BACKGROUND: The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area.Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. METHODS: We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. RESULTS: Sixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer. CONCLUSIONS: The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with gastric ulcer. In the southern Mexican population, the IL-1B -511C and -31T alleles and the -511C/-31T and -511T/-31T haplotypes are associated with increased risk of chronic gastritis and gastric ulcer.