BACKGROUNDCurrent knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.

METHODSWe recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated.

RESULTSAmong 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592), dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271), current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870), male gender (OR = 2.211, 95% CI: 1.027-4.760), GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278), and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669) were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding.

CONCLUSIONSPeptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

Aged ; Aspirin ; adverse effects ; Female ; Gastric Mucosa ; drug effects ; injuries ; Genotype ; Helicobacter Infections ; physiopathology ; Humans ; Male ; Middle Aged ; Peptic Ulcer ; physiopathology ; Platelet Aggregation Inhibitors ; adverse effects ; Polymorphism, Single Nucleotide ; genetics ; Risk Factors

OBJECTIVETo investigate the prevalence of cagA, vacA, and iceA genotypes in the isolated strains of Helicobacter pylori (H.pylori) from children with gastroduodenal diseases in Jiangxi, China, as well as the association between cagA, vacA, and iceA genotypes and the type of gastroduodenal diseases.

METHODSThe samples of gastric antral mucosa were collected from 316 children with gastroduodenal diseases in Jiangxi, and a total of 107 strains of H.pylori were isolated. The genomic DNA of these strains was extracted, and PCR was used to determine the ureA, cagA, vacA, and iceA genotypes.

RESULTSOf all the 107 isolated strains of H.pylori, the detection rates of ureA and cagA genes were 100% (107/107) and 94.4% (101/107) respectively. The overall detection rate of vacA gene was 100% (107/107), and the detection rates of vacAs1a, vacAs1c, vacAm1, and vacAm2 genes were 74.8% (80/107), 25.2% (27/107), 29.9% (32/107), and 69.2% (74/107) respectively, with both vacAm1 and vacAm2 genes detected in 0.9% (1/107) of all H.pylori strains. In the chimera of vacA gene, the detection rates of vacAs1a/m1, vacAs1a/m2, vacAs1c/m1, and vacAs1c/m2 genes were 26.2% (28/107), 51.4% (55/107), 3.7% (4/107), and 17.8% (19/107) respectively (P<0.001). The detection rates of iceA1 and iceA2 genes were 79.4% (85/107) and 9.3% (10/107), respectively (P<0.001), and both iceA1 and iceA2 genes were detected in 7.5% (8/107) of all strains. The detection rates of the genotypes of H.pylori showed no significant differences between the peptic ulcer, chronic gastritis, and duodenal bulbar inflammation groups (P>0.05).

CONCLUSIONSThe dominant genotypes of H.pylori are cagA, vacAs1a/m2, and iceA1, and there are mixed infections with H.pylori strains of different genotypes in children with gastroduodenal disease from Jiangxi, China. The genotypes of H.pylori are not associated with the type of gastroduodenal disease.

Adolescent ; Antigens, Bacterial ; genetics ; Bacterial Outer Membrane Proteins ; genetics ; Bacterial Proteins ; genetics ; Child ; Child, Preschool ; Female ; Gastritis ; microbiology ; Genotype ; Helicobacter pylori ; classification ; genetics ; isolation & purification ; Humans ; Infant ; Male ; Peptic Ulcer ; microbiology

No abstract available.
Female ; Gastric Mucosa/*metabolism ; Helicobacter Infections/*genetics ; Humans ; Male ; Peptic Ulcer/*genetics ; *Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/*genetics

BACKGROUND/AIMS: Tumor necrosis factor alpha (TNF-alpha) encoded by TNFA is a key mediator in inflammation, a precursor condition for peptic ulceration. Promoter polymorphisms of TNFA that influence its transcriptional activity and TNF-alpha production are known. TNFA-308G>A (rs1800629) and TNFA-1031T>C (rs1799964), which are responsible for increased TNFA transcription, could influence the risk of peptic ulceration. This study aimed to investigate these polymorphisms and to evaluate their association with peptic ulcer disease and Helicobacter pylori infection in the Polish population. METHODS: Gastric mucosa specimens obtained from 177 Polish peptic ulcer patients were used to conduct rapid urease tests and to assess the investigated polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data were compared with the results obtained from healthy individuals of Polish origin. RESULTS: There were no significant differences in genotype and allele frequency of the investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between the frequencies of particular genotypes and alleles for both single-nucleotide polymorphisms (SNPs) and the presence of H. pylori infection in peptic ulcer patients and in subgroups of men and women with peptic ulcer disease were found. CONCLUSIONS: The investigated SNPs are not risk factors for either peptic ulcer or H. pylori infection development in the Polish population. The results require verification in a larger cohort.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; European Continental Ancestry Group/genetics ; Female ; Gastric Mucosa/*metabolism/microbiology ; Genetic Predisposition to Disease ; Genotype ; Helicobacter Infections/complications/*genetics ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer/complications/*genetics ; Poland ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/*genetics ; Young Adult

BACKGROUND/AIMS: DNA double strand breaks (DSB) is one of the critical types of DNA damage. If unrepaired, DSB is accumulated in the nucleus of cells, the cells become apoptotic or transform to tumor by way of genomic instability. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. There was no report that Helicobacter pylori (H. pylori), the gastric carcinogen, induce DNA DSB in gastric epithelium in vivo. The aim of this study was to investigate whether H. pylori induce DSB in the gastric epithelial cells of chronic gastritis. METHODS: Immunohistochemical stains were performed for the DSB markers, phospho-53BP1 and gammaH2AX, in the gastric epithelium derived from 44 peptic ulcer disease patients before and after H. pylori eradication. DNA fragmentation assay was performed in the cell line to investigate the DNA damage by H. pylori infection. RESULTS: The mean expression score of gammaH2AX was significantly higher in the H. pylori infected gastric epithelium as compared to the H. pylori eradicated gastric epithelium (8.8+/-5.5 vs. 6.2+/-5.3 respectively; p=0.008). The expression score of phospho-53BP1 between before and after eradication of H. pylori was not statistically different, but tended to be higher in H. pylori infection. DNA fragmentation was developed significantly more in the cell lines after infection with H. pylori. CONCLUSIONS: DSB of DNA damage was typical feature of H. pylori infection in the gastric epithelium.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Cell Line, Tumor ; DNA/metabolism ; *DNA Breaks, Double-Stranded ; Female ; Gastric Mucosa/*metabolism ; Helicobacter Infections/drug therapy/*metabolism ; Helicobacter pylori/*drug effects/pathogenicity ; Histones/genetics/metabolism ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Male ; Middle Aged ; Peptic Ulcer/genetics/pathology

Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA s- and m- region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacA s1/m2 genotype and gastritis cases, and a significant correlation between vacA s1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacA s1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*genetics ; Bacterial Proteins/*genetics ; DNA, Bacterial/genetics ; Female ; Gastritis/genetics/microbiology/pathology ; Genotype ; Helicobacter Infections/*epidemiology/*microbiology/pathology ; Helicobacter pylori/*genetics/isolation & purification ; Humans ; Male ; Middle Aged ; Peptic Ulcer/genetics/microbiology/pathology ; Polymerase Chain Reaction ; Saudi Arabia ; Virulence Factors/genetics ; Young Adult

The size variation of the cytoxin-associated protein (cagA), which is dependent on the 3' repeat region (3'RR) of the cagA gene, is known to play a crucial role in the pathogenesis of Helicobacter pylori infection. The present study evaluated the relationship between the 3'RR variation and the geographic distribution, clinical manifestations, and locations of colonization in the stomach. We evaluated the 3'RR of H. pylori isolates from 78 patients with gastric cancer, peptic ulcer, and non-ulcer dyspepsia from Japan, Hong Kong, India, and the United States and assessed the variations of 3'RR according to the geographical and clinical characteristics. Sixty eight (87.2%) patients had the same 650 bp band without geographical differences. The frequency of polymorphisms in the 3'RR did not differ when compared to the clinical manifestations (P=0.868). The length of 3'RR did not differ by location of colonization. In conclusion, the 3'RR variation of cagA gene is not associated with the geographical and clinical characteristics of the patients studied.
Amino Acid Sequence ; Antigens, Bacterial/*genetics ; Bacterial Proteins/*genetics ; Dyspepsia/etiology ; Helicobacter Infections/diagnosis ; Helicobacter pylori/*genetics ; Humans ; Integration Host Factors ; Molecular Sequence Data ; Peptic Ulcer/etiology ; Polymorphism, Genetic ; Repetitive Sequences, Amino Acid ; Repetitive Sequences, Nucleic Acid ; Stomach Neoplasms/etiology

OBJECTIVETo investigate cagA, vacA and iceA genotypes of Helicobacter pylori (H. pylori) isolated from children suffering from gastric and duodenal diseases in Shanghai and to explore a possible genotype-phenotype correlation.

METHODSFrom May 2007 to January 2008, 59 children were confirmed with Hp infection by gastroscopy. Biopsied specimens were taken from the gastric antrum. cagA, vacA and iceA genes were determined by PCR. The histological changes in the gastric mucosa were evaluated. The levels of IFN-gamma and IL-4 in the gastric mucosa were measured using ELISA.

RESULTScagA, vacAs1/m1, vacAs1/m2, iceA1 and iceA2 were found in 65%, 19%, 40%, 63% and 19% of H. pylori strains, respectively. Both iceA1 and iceA2 were detected in 9% of strains. There were no statistical differences in the distribution of various genotypes between the children with chronic gastritis and peptic ulcer. No association was observed between the genotypes and the degree of inflammation of gastric mucosa. There were no significant differences in levels of IFN-gamma and IL-4 in the gastric mucosa infected by different genotypes of H. pylori strains.

CONCLUSIONScagA/vacAs1/m2/iceA1 may be the commonest genotype combination of H.pylori in children from Shanghai. That there was no association between H.pylori genotypes and clinical variables suggests the potential role of host and environment factors in the development of clinical diseases at a later life.

Adolescent ; Antigens, Bacterial ; genetics ; Bacterial Outer Membrane Proteins ; genetics ; Bacterial Proteins ; genetics ; Child ; Child, Preschool ; Female ; Gastritis ; microbiology ; Genotype ; Helicobacter pylori ; classification ; genetics ; Humans ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Male ; Peptic Ulcer ; microbiology

Extranodal NK/T-cell lymphoma is a recently recognized distinct entity within the World Health Organization classification of lymphoid tumors. It is relatively prevalent in Asian and South American populations. It most commonly occurs in the nasal or paranasal areas and less frequently in the skin, the soft tissue, and the gastrointestinal tract. Among these, extranodal NK/T-cell lymphoma of the gastrointestinal tract has shown an aggressive clinical course. We report a case of CD56+ extranodal NK/T-cell lymphoma presenting as a duodenal ulcer bleeding. A 62-year-old male patient presented with melena and abdominal pain. Endoscopic examination of the upper gastrointestinal tract showed the duodenal ulcer covered by blood clot. Pathologic examination revealed the diffuse infiltration of atypical lymphocytes with an angiocentric growth pattern, which was positive for CD3, CD56, and granzyme. The patient showed rapid deteriorating clinical course and died on day 14 after admission. Thus, we report this case with the review of literatures.
Antigens, CD3/metabolism ; Antigens, CD56/*metabolism ; Bone Marrow/pathology ; Duodenal Ulcer/*diagnosis ; Herpesvirus 4, Human/genetics/metabolism ; Humans ; Lymphoma, Extranodal NK-T-Cell/*diagnosis/pathology ; Male ; Middle Aged ; Peptic Ulcer Hemorrhage/*diagnosis ; Tomography, X-Ray Computed

BACKGROUNDAlmost half of the world's population suffer from the Helicobacter pylori (H. pylori) infection, but only some individuals develop gastric diseases with clinical symptoms. One reason for the phenomenon may be the different pathogenicity of infected H. pylori strains. The presence of cytotoxin-associated gene A (cagA) and expression of vacuolating cytotoxin activity encoded by vacuolating cytotoxin gene A (vacA) are considered the two major virulent markers of H. pylori. The aim of this study was to detect dominant cagA/vacA genotypes and coinfection frequency of H. pylori in patients with peptic ulceration (PU) or chronic gastritis (CG), and to determine correlations among different cagA/vacA genotypes, coinfection and severity of the diseases.

METHODSFor each of 139 patients in Zhejiang Province who had been diagnosed as PU or CG based on clinical symptoms and gastroscopy, two gastric biopsy specimens (one from antrum and the other from corpus) for H. pylori isolation were taken by two different disinfected biopsy forceps. One hundred and fifty-six H. pylori strains were isolated from both the antrum and corpus biopsy specimens of 78 patients (36 PU and 42 CG). PCRs were performed to detect cagA genes, and signal (s) and middle (m) regions of vacA genes in the H. pylori isolates. The amplified fragments of dominant vacA gene s and m subtypes from representative H. pylori isolates were sequenced after TA cloning. Dominant cagA/vacA genotypes of the H. pylori isolates, coinfection frequency and correlations among the different genotypes, coinfection and severity of the diseases were determined.

RESULTSOf the H. pylori strains isolated from the antrum specimens, 96.2% were cagA gene positive, as were 97.4% of the H. pylori strains isolated from the corpus specimens. Only one s region subtype (s1a) and four m region subtypes m1, m2, m1b and m1b-m2 of vacA gene were found. The proportions of vacA gene subtypes s1a/m1, s1a/m2, s1a/m1b and s1a/m1b-m2 in the 83 strains isolated from the antrum specimens were 7.2%, 61.5%, 30.1% and 1.2%, respectively, while those in the other 84 strains isolated from the corpus specimens were 9.5%, 58.3%, 28.6% and 3.6%, respectively. s1a/m2 (58.3% vs 30.1%, chi(2) = 13.47, P < 0.01) and then s1a/m1b (28.6% vs 9.5%, chi(2) = 9.88, P < 0.01) were the dominant vacA gene subtypes in the H. pylori isolates. The dominant H. pylori genotype was cagA + s1a/m2 (59.0% from antrum specimens and 57.1% from corpus specimens), and followed by cagA + s1a/m1b (28.9% from antrum specimens and 27.4% from corpus specimens). Sixteen of 78 patients (20.5%) were infected with two or three H. pylori strains with different genotypes. However, no statistically significant differences among cagA occurrence, the different vacA subtypes and PU or CG could be found (each P > 0.05). Similarities of the nucleotide sequences from vacA gene s region PCR products of six isolates and from vacA gene m region PCR products of four isolates were 93.2% to 98.3% and 93.8% to 97.6%, respectively, compared to the reported corresponding sequences.

CONCLUSIONSThe dominant genotypes of H. pylori in PU or CG patients in Zhejiang area may be cagA + s1a/m2 and cagA + s1a/m1b. Numerous coinfections with different H. pylori strains in PU or CG patients indicate diversity of the infected H. pylori origins. s and m regions of vacA gene from different H. pylori isolates show high nucleotide sequence similarities. cagA gene positive rate, different vacA gene subtypes and coinfection with different H. pylori strains are not closely associated with severity of the diseases.

Adult ; Amino Acid Sequence ; Antigens, Bacterial ; genetics ; Bacterial Proteins ; genetics ; Chronic Disease ; Female ; Gastritis ; microbiology ; Genotype ; Helicobacter Infections ; microbiology ; Helicobacter pylori ; classification ; genetics ; Humans ; Male ; Molecular Sequence Data ; Peptic Ulcer ; microbiology