Distinct <i>cagA</i> EPIYA Motifs are Associated with Ethnic Diversity in Malaysia and Singapore

Schmidt, H; Goh, Khean‐Lee; Fock, Kwong Ming; Hilmi, Ida; Dhamodaran, Subbiah; Forman, David; Mitchell, Hazel M.

doi:10.1111/j.1523-5378.2009.00684.x

Cited by 43 publications

(34 citation statements)

References 55 publications

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“…This result in the current study is in accordance to another study by Schmidt et al 20 showing significantly more Chinese isolates encoding the EPIYA-D motif. Besides the EPIYA motif, another study by Schmidt et al 21 has also shown significant variation of the prevalence of dupa and HP0521 allele with ethnicity.…”

Section: Discussionsupporting

confidence: 96%

Different cagA and vacA Polymorphisms are Found in the Chinese versus the Malay and Indian Populations: An Analysis of Helicobacter Pylori Virulence Genes in Singapore

Lui

Chuah

Goh

et al. 2010

Proceedings of Singapore Healthcare

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Aim:Helicobacter pylori causes peptic ulcer disease and gastric cancer. Western studies suggest that polymorphisms in the virulence factors caga and vaca may determine the ability of bacteria to cause gastroduodenal diseases. Differences in the caga EPIYA motifs and polymorphisms of the signal (s), middle (m) and intermediate (i) regions of vaca are thought to be important. The aim of this study was to compare the polymorphisms of caga and vaca of H. pylori isolated from the Chinese, Malay and Indian populations living in Singapore.Method: A total of 104 H. pylori isolates obtained from patients with dyspeptic symptoms were analysed. Of the 104 patients, 80 were Chinese, 9 Malays and 15 Indians. DNA was extracted from the isolates and the vaca allelic types and caga EPIYA motifs were determined by polymerase chain reaction (PCR) and sequencing, respectively. results: Differences in the vaca and caga polymorphisms were found between the Chinese, Malays and Indians. Significantly more non-Chinese patients carried vaca s1/m1 strains versus Chinese patients (p<0.05). All 9 Malay patients, 11/15 (73.3%) Indians and 31/80 (38.8%) Chinese patients carried H. pylori strains with the vaca s1/m1/i1. Significantly more Chinese patients carried isolates with East Asian caga EPIYA motifs versus nonChinese patients (p<0.05). 79/80 (98.8%) of the Chinese isolates, 2/15 (13%) of Indian isolates, and 5/9(55.6%) of Malay isolates possessed caga with the East Asian ABD type motif. Conclusion:Results from the current study demonstrated marked differences in the polymorphisms of vaca and caga EPIYA motifs in strains isolated from Chinese versus non-Chinese patients. Epidemiologically, the Chinese are at the highest risk of developing gastric cancer. Work is ongoing to determine if differences found in the caga EPIYA motifs of isolates from the Chinese patients can contribute to a subject's risk of developing gastric cancer.

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Section: Discussionsupporting

confidence: 96%

Different cagA and vacA Polymorphisms are Found in the Chinese versus the Malay and Indian Populations: An Analysis of Helicobacter Pylori Virulence Genes in Singapore

Lui

Chuah

Goh

et al. 2010

Proceedings of Singapore Healthcare

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“…It has been reported that in multiethnic societies, the distribution of cagA genotypes is not similar among different ethnic groups. For example, in Thailand, Malaysia, and Singapore, Eastern CagA is predominant among isolates from Chinese groups while Western CagA is predominant among isolates from Thais, Indians, and Malays (13,20,21,24). However, our method also has some disadvantages.…”

Section: Discussionmentioning

confidence: 91%

“…Such regions are found mostly in East Asia, including Okinawa, Thailand, Malaysia, and Singapore. (13,20,21,24). It has been reported that in multiethnic societies, the distribution of cagA genotypes is not similar among different ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Anti-East Asian CagA-Specific Antibody for CagA Phenotyping

Nguyen¹,

Uchida²,

Kuroda³

et al. 2009

Clin Vaccine Immunol

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The determination of the cagA genotype is generally based on sequencing the variable 3 region of the cagA gene. In a previous study, we successfully generated an anti-East Asian CagA-specific antibody (anti-EAS Ab) immunoreactive only with the East Asian CagA and not with the Western CagA. In a small number of Japanese patients, anti-EAS Ab appeared to be a useful tool for phenotyping CagA immunohistochemically. The present study was conducted to validate the anti-EAS Ab immunohistochemistry method in a larger number of patients from Vietnam and Thailand. A total of 385 Vietnamese and Thais were recruited. Helicobacter pylori status was determined by a combination of three methods, including culture, histology, and immunohistochemistry with anti-H. pylori antibody. The sensitivity, specificity, and accuracy of the anti-EAS Ab immunohistochemistry method for the diagnosis of CagA phenotype were calculated based on the results of the cagA sequencing as the gold standard. The sensitivity, specificity, and accuracy of our immunohistochemistry method were 96.7%, 97.9%, and 97.1%, respectively. Moreover, anti-EAS Ab was not cross-reactive with noninfected gastric mucosa. In conclusion, immunohistochemistry with anti-EAS Ab appears to be a good method for determination of CagA phenotype.

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“…Intriguingly, H. pylori strains carrying East Asian CagA (ABD-type CagA) are more closely associated with severe gastric atrophy and gastric carcinoma than are H. pylori strains carrying Western CagA (ABCn-type CagA) (29,30). Among H. pylori strains carrying Western CagA, those having CagA with a larger number of EPIYA-C segments are more likely to induce intestinal metaplasia and gastric carcinoma than are those having CagA with fewer EPIYA-C segments (31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of Helicobacter pylori CagA Protein Virulence through Homodimerization

Nagase

Murata‐Kamiya

Hatakeyama

2011

Journal of Biological Chemistry

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Background: H. pylori CagA oncoprotein is delivered into gastric epithelial cells, where it interacts with SHP2 oncoprotein and PAR1 kinase. Results: CagA dimerization stimulates the CagA-SHP2 interaction and thereby causes enhanced SHP2 deregulation. Conclusion: PAR1-mediated CagA dimerization plays an important role in the oncogenic activity of CagA. Significance: Inhibition of CagA dimerization has therapeutic value in preventing gastric carcinoma.

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Distinct cagA EPIYA Motifs are Associated with Ethnic Diversity in Malaysia and Singapore

Cited by 43 publications

References 55 publications

Different cagA and vacA Polymorphisms are Found in the Chinese versus the Malay and Indian Populations: An Analysis of Helicobacter Pylori Virulence Genes in Singapore

Different cagA and vacA Polymorphisms are Found in the Chinese versus the Malay and Indian Populations: An Analysis of Helicobacter Pylori Virulence Genes in Singapore

Evaluation of the Anti-East Asian CagA-Specific Antibody for CagA Phenotyping

Potentiation of Helicobacter pylori CagA Protein Virulence through Homodimerization

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