cagA Gene Research Articles

In silico Analysis of Virulence, Resistance Genes and Phylogeny of Helicobacter pylori Strains from Different Continents

Objective: Helicobacter pylori (H. pylori) is a bacterium that infects the gastric mucosa of 50% of the world population. It is known that different regional treatment practices used against the infections of H. pylori affect both the expression of virulence and antimicrobial resistance genes, giving the bacteria geographic differentiation. The aim of this study was to perform in silico analysis of virulence, resistance genes and phylogeny of H. pylori strains obtained from people living in different continents. Material and Method: Complete gene sequences of 18 H. pylori strains from six continents were downloaded from the National Center for Biotechnology Information (NCBI) database. The phylogeny of the strains, resistance and virulence genes were analyzed by CSI phylogeny, CARD and VFanalyzer, respectively. Results: African strains were the most distant identity to European strains. A2147G single nucleotide polymorphism associated with clarithromycin resistance was detected in South American and Asian origin. It was determined that strains were differentiated by a total of 95 related virulence genes under eight headings. The cagA, cagE, cagL and vacA genes were found in all strains in Asia. Conclusion: In conclusion, our study demonstrated that H. pylori strains, whose data were collected in different continents, differ from each other in terms of similarities and there is a serious difference especially in terms of virulence genes.

Correlation between clarithromycin resistance, virulence factors and clinical characteristics of the disease in Helicobacter pylori infected patients in Shahrekord, Southwest Iran

The purpose of this study was to determine the mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from biopsy samples that were collected from the endoscopic ward of Shahrekord Hajar teaching Hospital and also to study the frequency of virulence factor and their correlation and pathological findings with clarithromycin resistance during the years 2019–2020. In this cross-sectional descriptive study, 152 patients with Helicobacter pylori infection were considered, and then, two common A2142G and A2143G mutations in the 23SrRNA gene associated with resistance were analyzed by Real-time PCR (Taq man). The presence of vacA, iceA1, iceA2, cagA, babA2, and oipA virulence genes was investigated by PCR and electrophoresis in 8% polyacrylamide gel. Then, data were analyzed using the relevant statistical tests. In this study, the frequency of Helicobacter pylori was 76% and the frequency of mutant isolates was 57.2%. The frequencies of A2142G and A2143G point mutations were 42.1% and 28.3%. There was a significant correlation among oipA, vacA, and iceA1 virulence factors, type of disease, chronic inflammatory score, and glandular atrophy with the antibiotic resistance to clarithromycin. There was no significant correlation between the age and sex of the patients with antibiotic resistance. According to the results of this study, it seems that the use of clarithromycin to combat this bacterium should be limited.

Molecular detection of the virulence gene’s VacA and CagA of Helicobacter pylori by PCR

Helicobacter pylori has several virulence factors, including the ability to produce urease, which allows it to colonize the stomach and survive for long periods of time. As a results of those virulence factors of H. Pylor i causes gastritis. This study aimed to detect H. pylori using of real-time PCR amplification of VacA and CagA genes, and compare between both genes and detection by urease and creatine. For this purpose, a total of 50 patients were selected and have been clinically diagnosed with gastritis. Biopsy samples were collected from all the patients. Rapid urease test (RUT) was applied to all gastric samples to detect the presence of H. Pylori . DNA was extracted and the RT-PCR was perform to detect the VacA and CagA genes. The results of RUT showed 20 samples were positive of H. Pylori , after the Real Time-PCR test were done the results showed 27 (54%) to VacA and 25 (50%) to CagA genes were positives.

HELICOBACTER PYLORI cagA VIRULENCE GENE AND SEVERE ESOGASTRODUODENAL DISEASES: IS THERE AN ASSOCIATION?

Helicobacter pylori colonizes approximately half of the world's human population. Its presence in the gastric mucosa is associated with an increased risk of gastric adenocarcinoma, gastric lymphoma, and peptic ulcer disease. In Brazil, the high prevalence of H. pylori infection is a serious health problem. H. pylori virulence factors are associated with an increased risk of serious gastrointestinal disorders. The cagA gene encodes a cytotoxin-A-associated antigen (CagA) that is involved in bacterial pathogenicity. H. pylori strains carrying the cag pathogenicity island (cag-PAI) are significantly associated with severe clinical outcomes and histopathological changes. The present study aims to investigate the prevalence of the cagA gene among H. pylori isolates from patients with different gastric pathologies. Further, the study hopes to verify its association with clinical outcomes. In addition, phylogenetic analysis was performed on cagA-positive H. pylori strains from patients with severe and non-severe diseases. Gastric specimens were collected through a biopsy from 117 patients with different esogastroduodenal diseases. DNA was extracted from these gastric specimens and the polymerase chain reaction was performed to amplify the gene fragments corresponding to the 16S ribosomal RNA and cagA genes using specific primers. The polymerase chain reaction products of selected samples positive for cagA were sequenced. The sequences were aligned with reference sequences from the National Center for Biotechnology Information (NCBI) (Bethesda/USA), and a phylogenetic tree was constructed. H. pylori was detected in 65.9% (77/117) of Brazilian patients with different gastroduodenal disorders. Overall, 80.5% (62/77) of the strains were cagA-positive. The ages of patients with cagA-positive strains (15 males and 47 females) ranged from 18 to 74 years. The lesions were categorized as non-severe and severe according to the endoscopic and histopathological reports the most prevalent non-severe esogastroduodenal lesion was gastritis 54/77 (70.12%), followed by esophagitis 12/77 (15.58%) and duodenitis 12/77 (15.58%). In contrast, the most prevalent severe lesions were atrophy 7/77 (9.09%), followed by metaplasia 3/77 (3.86%) and gastric adenocarcinoma 2/77 (2.59%). Phylogenetic analyses performed with the partial sequences of the cagA gene obtained from local strains were grouped in the same clade. No differences in phylogenetic distribution was detected between severe and non-severe diseases. The cagA gene is highly prevalent among H. pylori isolates from gastric lesions in Brazilian patients. The presence of the cagA gene was not considered a marker of the severity of esogastroduodenal lesions in the present study. This is the first study to investigate the phylogenetic population structure of H. pylori strains in a Brazilian capital, which may improve our understanding of the clinical outcome of H. pylori infection.

The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins

BackgroundThe burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam.ResultsThere are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively.ConclusionsThere are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters.

Individual hosts carry H. pylori isolates with different cagA features - motifs and copy number.

H. pylori strains with different genetic contents may infect different or an individual human host. Genetic diversity of cagA is thought to contribute to differences in H. pylori strains pathogenicity. In this study, diversity of cagA genotype, EPIYA motif and copy number was assessed in H. pylori single colonies isolated from individual patients. Gastric biopsies from 14H. pylori-positive dyspeptic patients were cultured on selective brucella blood agar and incubated at 37°C under microaerobic conditions. Four single colonies were obtained from each biopsy subculture on brucella blood agar under similar incubation condition. Presence of cagA and types of EPIYA motifs was determined by polymerase chain reaction (PCR) and cagA copy number by quantitative real-time (RT) PCR. Single colonies of 5 patients showed no variation in cagA genotype, EPIYA motif and copy number. Out of the remaining 9 patients, 1 patient showed presence or absence of cagA gene, 2 patients had mixed EPIYA motifs, 2 patients had different cagA copy number, 1 patient showed absence or presence of cagA and mixed motifs, 2 patients had cagA genes with different nucleotide sequences, 1 patient showed presence or absence of cagA and difference in cagA nucleotide sequence. Four isolates that contained multiple copies of cagA, carried EPIYA-ABC motif. Genetic diversity of cagA among single colonies isolated from individual patients represents evidence that gastric mucosa of every individual is colonized with a specific and heterogeneous population of H. pylori. Future studies on patients in different disease groups may elucidate the role of mixed populations of H. pylori in development of gastric diseases.

The relationship between the simultaneity present of cagA and hopQI genes in Helicobacter pylori and the risk of gastric cancer.

Helicobacter pylori is a bacterium that causes infections in the gastrointestinal tract. This type of bacterium is very common and contagious at the same time. H. pylori enters the mouth and continues its course along the gastrointestinal tract. H. pylori infection induces an inflammatory response that leads to the activity of neutrophils, lymphocytes, plasma cells, and macrophages. In addition to the bacterial role in gastric mucosa, the host's inflammatory response may also play a role in disease outcome. In inflammation, the risk of carcinogenesis increases due to DNA damage increased proliferation and the creation of an environment rich in cytokines and growth factors. Genetic methods and diagnosis of H. pylori genes are used to identify healthy and healthy gastric cancer patients infected with H. pylori. In relation to the genes associated with H. pylori pathogenesis, the presence of genes such as cagA, hopQI, hopQII and so on is used, and PCR of a part of these genes amplified fragments of different lengths. One of the less-studied cases is the association of two or more pathogenic genes simultaneously with H. pylori. In this research, the frequency of disease and healthy individuals who are infected with H. pylori and have two genotypes cagA and hopQI at the same time, was examined. In order to diagnose H. pylori-infected individuals in healthy and gastric cancer patients, after PCR of glmM gene, PCR product electrophoresis on agarose gel was used. For this purpose, gastric tissue biopsy was used in patients and saliva was used in healthy individuals. For this purpose, 100 gastric biopsy samples were collected from patients with gastric cancer and 100 saliva samples from healthy individuals. According to the data, there is a significant relationship between the simultaneous presence of two genes cagA and hopQI and gastric cancer. In patients, 45.3% showed both genotypes, while in healthy individuals only 10.5% have this genotype and other healthy but infected with H. pylori (90.8%) do not have this genotype. To be. No report was observed on the simultaneous study of cagA and hopQI genes. No report was observed regarding the simultaneous study of cagA and hopQI genes.

Frequency of virulence-associated genotypes of Helicobacter pylori and their correlation with clinical outcome and histological parameters in infected patients

Helicobacter pylori (H. pylori) is a gram-negative which can cause several gastroduodenal diseases, including gastritis and peptic ulcer disease (PUD). H. pylori specific genotypes have been related to increased occurrence of gastritis and PUD. The aim of this study was to investigate the clinical relevance of the major virulence factors of H. pylori with clinical outcomes and histological parameters in Iranian patients. Totally, 200 subjects with PUD and gastritis disease who underwent gastroduodenal endoscopy were enrolled in this study. The presence of the cagA, vacA, oipA, babA2, and iceA genes in antral gastric biopsy specimens were determined by polymerase chain reaction (PCR) and the results were compared with clinical outcomes and histological parameters. The frequency of babA2+, oipA+, vacA s1/m2, and vacA m2 genes was significantly higher in patients with peptic ulcer disease compared with patients with gastritis. In contrast, the frequency of vacA s1/m1 gene was significantly higher in gastritis subjects than PUD subjects. The high-density scores of H. pylori were strongly associated with iceA1¯, babA2+, and oipA+ genes. Additionally, the high polymorphonuclear cell infiltration and high mononuclear cell infiltration scores were strongly associated with the cagA+, iceA1¯, oipA+ genes and cagA+, babA2+, oipA+ genes, respectively. Our study indicated that the vacA, babA2, and oipA virulence factors are related to a higher risk of PUD in subjects with H. pylori-infection. Infection with these strains was associated with a more severe gastropathy.

Determine the Prevalence of cagA and Baba of Helicobacter Pylori Isolated from Gastric Atrophic Patients

Objective: The aim of this study is to determine the prevalence of cagA and babA of helicobacter pylori isolated from gastric atrophic patients. Study Design: Descriptive/Analytical Place and Duration: The study was conducted at Medicine/Gastroenterology department of Khyber Teaching Hospital and Peshawar Institute of Medical Sciences, Peshawar for six months duration from March 2020 to August 2020. Methods: Total one hundred and twenty patients of both genders were presented in this study. Patients were aged between 20-80 years of age. Patients detailed demographics age, sex and body mass index were recorded after taking informed written consent. All patients of gastroduodenal disorders were undergone for isolation of bacteria by using standard techniques. Complete data was analyzed by SPSS 22.0 version. Results: Total 50 (41.7%) patients were males and 70 (58.3%) patients were females. Mean age of the patients were 41.96 ± 16 years with mean BMI 25.24 ± 4.8 kg/m2. Frequency of H pylori was isolated in 30 (25%) patients in which 13 patients had atrophic gastritis, 9 patients had gastric ulcer and 8 patients had acute gastritis. Prevalence of cagA gene was 16 (53.33%) and babA was 10 (33.33%) in H. pylori isolated patients. Significantly difference with p value <0.05 was observed between cagA positive strains and patients of gastric atrophic. The involvement of gastric atrophic patients was not correlated to the babA gene. Conclusion: We concluded in this study that different cagA positive H. pylori can be retrieved from gastric atrophy patients. Keywords: Gastric atrophy, Gastric cancer, cagA, babA, Helicobacter pylori

Genotyping of Helicobacter pylori Virulence Genes cagA and vacA: Regional and National Study.

Helicobacter pylori (H. pylori) plays a crucial role in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The presence of pathogenicity islands (PAI) genes contributes to the pathogenesis of many gastrointestinal disorders. Cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene (vacA) are the most known virulence genes in H. pylori. So, our aim was to study H. pylori virulence genes' role in gastric disorders pathogenesis. Our study included 150 adult patients who suffered dyspeptic symptoms and were referred to the GIT endoscopy unit. Gastric biopsies were attained for rapid urease test (RUT) and histopathological examination, and multiplex PCR technique for detection of virulence genes was performed. It was found that 100 specimens were (RUT) positive, of which sixty samples (60%) were PCR positive for H. pylori ureC gene. The vacA and cagA genes were identified in 61.6% and 53% of H. pylori strains, respectively. Only 5 cases were vacA-positive and cagA-negative. The most virulent vacA s1 allele existed in 56.6% of cases. Out of the 60 H. pylori strains, 66% had at least one virulence gene and 34% did not show any virulence gene. H. pylori infection showed significant increase with age. H. pylori are prevalent amid dyspeptic patients in our region. The main genotype combinations were vacA+/cagA+ of s1m1 genotype and they were frequently associated with peptic ulcer diseases, gastritis, and gastroesophageal reflux disease.

Geographic distribution of the cagA, vacA, iceA, oipA and dupA genes of Helicobacter pylori strains isolated in China

BackgroundThere are geographic variations in the genotypes of Helicobacter pylori (H. pylori) cagA, vacA, iceA, oipA and dupA. The aim of the study was to investigate the distribution of these genotypes among H. pylori strains from five regions of China and their association with clinical outcomes.Materials and methodsGastric biopsy specimens were obtained from 348 patients with different gastrointestinal diseases in the five regions of China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. The presence of cagA, vacA, iceA, oipA and dupA genotypes was determined by polymerase chain reaction (PCR) from H. pylori DNA.ResultsA total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA-positive status was predominant in the five regions. The predominant vacA genotypes were s1c (73.4%), m2 (70.6%) and i1 (92.9%). In strains from Shandong, s1a and m1 were dominant. By contrast, s1c was dominant in Guangxi and i1 was dominant in Hunan and Heilongjiang. The prevalence of m2 subtype in Qinghai (78.8%) was significantly higher than that in other regions (P < 0.05). The predominant iceA genotype was iceA1 and the frequency of iceA1 was significantly more prevalent in Hunan than in other regions (P < 0.05). The oipA status “on” gene was more frequent in Shandong (91.9%) and Guangxi (91%) than in Heilongjiang (71.7%) (P < 0.05). Conversely, the dupA-positive status was less than half in Shandong (31.1%) and Guangxi (15.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (P < 0.001). There were no significant associations between the cagA, vacA, iceA, oipA genotypes and clinical outcomes. The dupA-positive strains were more common in peptic ulcer disease (PUD) patients than in non-ulcer dyspepsia (NUD) patients in Shandong and Guangxi (P < 0.05), but the association was not observed in other geographic regions.ConclusionsThere was significant geographic diversity of H. pylori genotypes in different regions of China and the presence of dupA gene can be considered as a marker for the development of gastroduodenal diseases. However, the cagA, iceA, vacA and oipA genes cannot be regarded for prediction of the clinical presentation of H. pylori infection in China.

The relationship between the presence of Helicobacter pylori and the composition of ionic and organic microelements in drinking water from Cracow.

Although the natural niche for H. pylori (Hp) is the human stomach, for widespread infection to occur this microorganism may need to survive in the external environment. Molecular techniques such as polymerase (PCR) have revealed the presence of Hp DNA in water, indicating that this environment could act as a reservoir for this bacterium. The aim of this study was to analyse the occurrence of Hp in tap water from Cracow and to examine the relationship between 26 parameters and the presence of Hp DNA due to the lack of such information related to this issue in Poland. Additional aim of this study was to determine whether the correlation between Hp DNA detection and seasonal changes of water quality in 379 water samples collected from various water treatment plants (WTPs), could be found. Water samples were subjected to PCR for glmM and cagA genes. Ionic and organic composition of microelements were determined in accordance to Polish and ISO standards. The data obtained from tests show that 212 (55.96%) objects were Hp DNA (glmM) positive and among them 145 (68.40%) waters samples revealed expression of cagA. Linear Discriminant Analysis and Principal Component Analysis were used and provided that the selected variables (p < 0.05): colour, pH, conductivity at 25°C, chlorides, nitrites, nitrates, phosphates, chlorates, chlorites, sulphates, free chlorine, sodium, magnesium, potassium, calcium, organic carbon, trichloromethane, bromodichloromethane, dibromochloroethane, total iron, ammonium ion, and ƩTMHs distinguished the water samples that contain Hp DNA and do not contain Hp DNA. We conclude that the ionic and organic composition of microelements in water might influence the presence of Hp. Thus, determination of the selected microelements may indirectly indicate or sometimes predict the presence of Hp in drinking water.

The Prevalence of H. Pylori cagA Gene in Patients with Gastric Ulcer

The Prevalence of H. Pylori cagA Gene in Patients with Gastric Ulcer

VIRULENCE PROFILE OF HELICOBACTER PYLORI DETECTED IN GASTRIC BIOPSIES OF PATIENTS UNDERGOING ENDOSCOPY IN UPPER EGYPT

Background: Helicobacter pylori (H. pylori) is a common cause of gastric ulcers and is a risk factor for gastric carcinoma. Little data are available about the characters of H. pylori causing infections in patients from Upper Egypt. Therefore, the aim of this study was to investigate the frequency of H. pylori infection in Egyptian patients undergoing endoscopy and complaining of persistent upper gastrointestinal symptoms directly in biopsy specimens using PCR technique and to study the associated virulence-related genes in H. pylori positive samples. Materials and Methods: One hundred and twenty gastric biopsy specimens were collected from Egyptian patients admitted to Assiut University Hospital and complaining of persistent upper gastrointestinal symptoms. H. pylori DNA was extracted for molecular identification by PCR. Positive samples were further analyzed to investigate the presence of different virulence-related genes and gene combinations. Results: H. pylori was detected in 92/120 (76.6%) of collected biopsies. All strains carried the vacA s1 subtype. The prevalence of the virulence genes cagA, cagE, iceA1, iceA2 and oipA were 79 (84.8%), 41(44.5%), 69 (75%), 44 (47.8%), and 55(59.7%) of the H. pylori positive samples, respectively. Genetic analysis showed that H. pylori were grouped into 29 different genotype combinations. The s1/m1/i1/d1/c1/cagA/iceA1/oipA genotype was the most predominant. Conclusion: Our results show a high frequency of H. pylori infections among Egyptian patients with gastrointestinal symptoms. The s1/m1/i1 vacA hybrid is the most prevalent subtype. The distribution of the different virulence-related genes shows alarming rates of cagA, cagE, iceA1, iceA2 and oipA. Careful monitory of H. pylori infections and investigation of their genetic characters should be carried out to control the spread of the virulent strains.

H. pylori infection induces CXCL8 expression and promotes gastric cancer progress through downregulating KLF4

Tumour-derived CXCL8 facilitates the movement of myeloid-derived suppressor cells, which are able to restrain antitumour immune responses to the tumour microenvironment. Kruppel-like factor 4 (KLF4) is a potential tumour suppressor in gastric cancer (GC). However, knowledge regarding correlations between KLF4 and CXCL8 in GC is limited. We use cellular and molecular biological methods to assess whether these two factors interact in GC. Expression CXCL8 and KLF4 was altered in human GC tissues compared to normal gastric tissues in opposite ways. Additionally, cytotoxin-associated gene A protein (CagA) gene transduction or Helicobacter pylori(H. pylori) infection upregulated CXCL8 expression. Knockdown of KLF4 expression increased CXCL8 protein and RNA expression, whereas its overexpression had the opposite effect. CXCL8-mediated enhancement of GC cell migration and proliferation was reversed by upregulation of KLF4 expression. Further mechanistic research revealed that KLF4 binds the CXCL8 promoter, suppressing CXCL8 transcription. Moreover, CXCL8 stimulation reduced KLF4 protein expression and promoted GC cell proliferation and migration, eventually promoting neoplasm growth in vivo. Together, our findings demonstrate that CagA promotes CXCL8 and inhibits KLF4. CXCL8 is a decisive downstream target gene of KLF4, and KLF4 negatively regulates CXCL8 in GC. Furthermore, CXCL8's negative regulation of KLF4 in vivo and in vitro, indicates that CagA may downregulate KLF4 by inducing CXCL8 expression, low expression of KLF4 further promotes that of CXCL8, forming a vicious circle in GC. Targeted KLF4 activation might improve the immunosuppressive microenvironment through direct negative regulation of CXCL8, providing a new potential target to strengthen the efficacy of immunotherapy in GC patients.

Evaluation of Helicobacter pylori Genotypes in Obese Patients with Gastric Ulcer, Duodenal Ulcer, and Gastric Cancer: An Observational Study

Introduction: Obesity is a well-known risk factor for a variety of gastrointestinal disorders (GID). Helicobacter pylori is associated with different GID, such as gastric cancer and chronic gastritis. In this study, we investigated the prevalence of dominant genotypes in H. pylori isolated from obese patients diagnosed with gastric ulcer, duodenal ulcer, and gastric cancer. Methods: A total of 222 H. pylori-positive samples were collected from patients with obesity. GID and gastric cancer were identified by endoscopy and histopathology, respectively. Three biopsy specimens from the gastric antrum were obtained from each patient for culture tests, histological examination, and identification of vacuolating cytotoxin A (vacA) (vacA s1, vacA s2, vacA m1, vacA m2, vacA s1m1 vacA s1m2, vacA s2m1, and vacA s2m2), cagA, cagE, iceA1, oipA, dupA, and babA2 using polymerase chain reaction. Results: vacA, cagE, cagA, iceA1, oipA, dupA, and babA2 genes were detected in 222 (100%), 171 (77%), 161 (72.5%), 77 (34.6%), 77 (34.6%), 137 (61%), and 69 (31%) patients with obesity, respectively. Our findings revealed that vacA, iceA1, oipA, and babA2 were significantly associated with a higher risk of GID, while cagE, cagA, and dupA indicated no correlation with the development of GID. Also, in the combination of s- and m-region genotypes, s1m2 (79%) was the most frequently identified genotype in patients with obesity. A significant association was also found between cagA and the presence of vacA genotypes (except for vacA m1 and babA2). Conclusions: This study indicated the high prevalence of different virulence genes in H. pylori isolated from obese patients and supported the significant role of H. pylori in the development of GID.

Prevalence of tumor necrosis factor alpha inducing protein (tipα) gene of Helicobacter pylori and its association with upper gastrointestinal diseases in India.

Helicobacter pylori (H. pylori) is known to cause several gastroduodenal diseases including chronic Gastritis, Peptic Ulcer disease and Gastric Cancer. Virulent genes of H. pylori like cagA, vacA are known to be responsible for the disease pathogenesis. However, these virulence genes are not always found to be associated with disease outcome in all populations around the world. Tumor necrosis factor alpha inducing protein tipα is a newly discovered virulence gene of H. pylori and is an inducer of certain cytokines and chemokines that are responsible for causing stomach cancer. Therefore, we conducted a study, which aims to find the prevalence of tipα gene in the Indian patients with gastroduodenal symptoms, and its association with H. pylori related gastroduodenal diseases. 267 clinical H. pylori isolates are included in our study for finding the prevalence of tipα gene and its association with cagA and vacA gene using PCR assay. The current study shows that the prevalence rate of tipα gene is 59.9%. Our study has found a significant association (p < 0.05) of tipα gene with Non Ulcer Dyspepsia (NUD) and an association of cagA and vacAs1m1 with Gastritis and Duodenal Ulcer. Our study demonstrates for the first time the presence of tipα as virulence factor of H. pylori strain in Indian population isolated from patients suffering from gastroduodenal diseases. Further, tipα is significantly associated with NUD but not with other gastroduodenal diseases in India.

Contribution of genetic polymorphisms of interleukins IL1B-511 C/T, IL1RN VNTR, IL6-174 G/C, and IL8-251 A/T in gastric lesions: gender and Helicobacter pylori genes matter.

Stomach pathologies develop in a complex interaction between the host's genetic background and H. pylori virulent genes. Thus, our study aimed to compare active chronic gastritis (ACG), and intestinal metaplasia (IM) with inactive chronic gastritis (ICG), according to interleukin polymorphisms of IL6-174 G/C, IL8-251 A/T, IL1β-511 C/T, and IL1RN VNTR taking into account patient gender and H. pylori genotypes. Interleukin polymorphisms were determined by RFLP-PCR and H. pylori genotype by PCR. IL6-174 GC and IL8-251T allele showed a protective effect in women against ACG development and, conversely, IL8-251 polymorphism showed a risk for men. More virulent H. pylori strains were associated with the IL8-251T allele and IL1β-511T allele in the AGC, and the vacA m1allele and cagE gene from H. pylori was associated with the IM. Analysis of the progression of gastric lesions must take into account host variability genetic associated with genes H. pylori due to the relation between the virulent H. pylori genes and more severe gastric lesions, besides the relevance to the gender to IL6-174 and IL8-251 polymorphisms.

Diversity of 3\u2032 variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

BackgroundThe cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases.MethodsA total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software.ResultsA total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004).ConclusionsIn this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

Helicobacter Pylori Variants with ABC-Type Tyrosine Phosphorylation Motif in Gastric Biopsies of Ghanaian Patients.

Background Helicobacter pylori pathogenicity and disease severity are determined by the tyrosine phosphorylation motifs of CagA protein. This study is aimed at detecting the presence of H. pylori and identifying the CagA tyrosine phosphorylation motifs in Ghanaian patients. Material and Methods. A total of 94 archival genomic DNA samples from gastric biopsies were used for the study, and H. pylori was detected by amplifying the 16S rRNA gene. The 3′-end variable region of the cagA gene was amplified, and the entire 3′-end was sequenced and translated into amino acids. Results H. pylori was detected in 53.2% (50/94) of the samples, and all the detected bacteria harboured the cagA gene. Two variants of the bacteria were identified based on the size of the amplified cagA gene: 207 bp and 285 bp. The 207 bp and 285 bp variants accounted for 74% and 22%, respectively, and 4% showed both fragments. Translated amino acid sequence of the cagA gene showed EPIYA-A, EPIYA-B, and EPIYA-C (ABC type) motifs, indicating the Western variant. The CagA protein C-terminal showed insertion of amino acids in the sequence flanking the EPIYA-A motif at the N-terminal and a complete deletion of the EPIYA-CC and EPIYA-CCC motifs together with the flanking sequences. Conclusions H. pylori identified were Western variant (ABC type) with unique amino acid insertions, suggesting unique variants in Ghanaian patients. Further investigation is however required to understand the role of the molecular diversity of the variant in gastric disease outcome.