Helicobacter pylori with East Asian-type cag PAI genes is more virulent than strains with Western-type in some cag PAI genes

Yuan, Xiaoyan; Yan, Jin-Jun; Yang, Yachao; Wu, Chun-mei; Hu, Yan; Geng, Jiawei

doi:10.1016/j.bjm.2016.12.004

Cited by 21 publications

(12 citation statements)

References 23 publications

(28 reference statements)

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“…East Asian-type cagA is more virulent than Western-type cagA due to its stronger binding affinity for SHP2 and morphological transforming activities [41]. In agreement with Yuan et al, mucosal inflammation was significantly higher in patients infected with East Asian-type cagA strains in in vitro and in vivo studies, and East Asian-type cagA strains appear to be a major contributor to clinical severity and gastric carcinogenesis as compared with Western-type cagA [12]. Our findings are supported by a previous study that showed that H. pylori cagA sequences from a Korean population were associated with East Asian-type cagA (ABD) [42], while most of the cagA sequences from Thai patients were identified as Western-type cagA (ABC).…”

Section: Discussionsupporting

confidence: 85%

“…Several published studies demonstrated that more than 90% of H. pylori strains from East Asian populations carry the cagA gene [10,11], but approximately 20-40% of strains from other regions are cagA negative. Based on the conserved five-amino acid repeat motif (EPIYA motif) at the carboxyl terminal, CagA is classified into two major genotypes: Western type and East Asian type; however, the genotype of East Asian CagA is closely linked with development of gastric cancer [12].…”

Section: Introductionmentioning

confidence: 99%

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Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand

et al. 2020

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There is a lack of evidence of genetic variation in the Helicobacter pylori cag-PAI in Thailand, a region with the low incidence of gastric cancer. To clarify this issue, variation in the H. pylori cag-PAI in strains detected in Thailand was characterized and simultaneously compared with strains isolated from a high-risk population in Korea. The presence of ten gene clusters within cag-PAI (cagA, cagE, cagG, cagH, cagL, cagM, cagT, orf13, virB11, and orf10) and IS605 was characterized in H. pylori strains detected from these two countries. The cagA genotypes and EPIYA motifs were analyzed by DNA sequencing. The overall proportion of the ten cag-PAI genes that were detected ranged between 66 and 79%; additionally, approximately 48% of the strains from Thai patients contained an intact cag-PAI structure, while a significantly higher proportion (80%) of the strains from Korean patients had an intact cag-PAI. A significantly higher proportion of IS605 was detected in strains from Thai patients (55%). Analysis of cagA genotypes and EPIYA motifs revealed a higher frequency of Western-type cagA in Thai patients (87%) relative to Korean patients (8%) who were predominately associated with the East Asian-type cagA (92%). Variations in the Western-type cagA in the Thai population, such as EPIYA-BC patterns and EPIYA-like sequences (EPIYT), were mainly detected as compared with the Korean population (p < 0.05). In summary, H. pylori strains that colonize the Thai population tend to be associated with low virulence due to distinctive cag-PAI variation, which may partially explain the Asian paradox phenomenon in Thailand.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand

et al. 2020

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“…Over and above different methods of ascertaining IP- and Helicobacter -status, the risk of the two being associated appeared considerably higher in Taiwan [ 65 ] than in Denmark [ 63 ]. This may relate to greater virulence conferred by East Asian-type cag pathogenicity island genes (manifest as gastric mucosal inflammatory cell infiltration; secretion of the pro-inflammatory cytokine, interleukin-8; and translocation of CagA into host cells) [ 75 ]. Even in Europe, a particular profile of antibodies against pathogenicity markers is predictive of the current disease burden and deterioration of IP over time [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism

Tucker

Augustin

Hayee

et al. 2020

JCM

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Interest in an aetiopathogenic role for Helicobacter in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of Helicobacter and IP, the benefits of eradicating Helicobacter in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of Helicobacter eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between Helicobacter and IP is well-established. H. pylori virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful H. pylori eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of H. pylori at molecular level only. Adequate prognostic assessment of the consequences of not treating Helicobacter, for IP, is prevented by a short follow-up. We conclude that Helicobacter is a pathophysiological driver of IP.

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“…Bacterial virulence factor is one of the contributing factors to the development of severe H. pylori-related diseases. The diversity of cagPAI region in the H. pylori genome may have a modifying effect on the pathogenic potential of the infecting strain [24].…”

Section: Discussionmentioning

confidence: 99%

The organization of Helicobacter pylori cag-pathogenicity island (cagPAI) genes in multiracial population with histopathological changes of gastric mucosa

Hanafiah

Razak

Neoh

et al. 2019

Preprint

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Background: Helicobacter pylori is a Gram-negative bacillus that colonises only the mucus layer of the human stomach and is implicated in gastric diseases. Virulent H. pylori harbouring cag-pathogenicity island (cagPAI) which encodes genes for type IV secretion system (T4SS) and CagA protein is one of the major virulence determinants involved in disease development. We examined the entire cagPAI genes in 95 H. pylori isolates from a multiracial population and examined the intactness of cagPAI region with histopathological scores of the gastric mucosa. Results: 95.8% of H. pylori isolates were cagPAI-positive with 23.2% having an intact cagPAI, whereas 72.6% had a partial/rearranged cagPAI. In our study, cag2 and cag4 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominant in Chinese isolates. We also detected cag24 in significantly high proportion in isolates from the Malays and the Indians compared to the Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI and higher density of H. pylori and neutrophil activity, whereas strains which lacked cagPAI was associated with higher inflammatory score. Conclusions: The screening of the entire cagPAI genes provides an accurate overview of the cagPAI organisation in H. pylori isolates in a multiracial population. The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients’ ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.

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Helicobacter pylori with East Asian-type cag PAI genes is more virulent than strains with Western-type in some cag PAI genes

Cited by 21 publications

References 23 publications

Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand

Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand

Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism

The organization of Helicobacter pylori cag-pathogenicity island (cagPAI) genes in multiracial population with histopathological changes of gastric mucosa

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