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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A New Helicobacter pylori Vacuolating Cytotoxin Determinant, the Intermediate Region, Is Associated With Gastric Cancer
Gastroenterology, Volume 133, No. 3, Year 2007
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Description
Background & Aims: Helicobacter pylori is the main cause of peptic ulceration and gastric adenocarcinoma. The vacuolating cytotoxin gene, vacA, is a major determinant of virulence. Two naturally polymorphic sites in vacA, the signal region and midregion, are well-characterized determinants of toxicity and markers of pathogenesis. The aim of this study was to characterize a new vacA polymorphic site, the intermediate (i) region. Methods: The vacA i-region was identified and characterized by constructing isogenic vacA exchange mutants and determining their vacuolating activity on HeLa, AGS, and RK13 cell lines. The vacA i-region types of H pylori isolates from patients undergoing routine endoscopy were determined by nucleotide sequencing and allele-specific polymerase chain reaction. Results: Two i-region types were identified, i1 and i2, and both were common among 42 Western clinical isolates. Interestingly, only naturally occurring s1/m2 strains varied in i-type; s1/m1 and s2/m2 strains were exclusively i1 and i2, respectively. Vacuolation assays showed that i-type determined vacuolating activity among these s1/m2 strains, and exchange mutagenesis confirmed that the i-region itself was directly responsible. Using a simple i-region polymerase chain reaction-based typing system, it was shown for 73 Iranian patients that i1-type strains were strongly associated with gastric adenocarcinoma (P < 10-3). Finally, logistic regression analysis showed this association to be independent of, and larger than, associations of vacA s- or m-type or cag status with gastric adenocarcinoma. Conclusions: Together these data show that the vacA i-region is an important determinant of H pylori toxicity and the best independent marker of VacA-associated pathogenicity. © 2007 AGA Institute.
Authors & Co-Authors
Rhead, Joanne L.
United Kingdom, Nottingham
University of Nottingham
Letley, Darren P.
United Kingdom, Nottingham
University of Nottingham
Mohammadi, Marjan
Iran, Tehran
Pasteur Institute of Iran
Hussein, Nawfal Rasheed
United Kingdom, Nottingham
University of Nottingham
Iraq, Duhok
University of Duhok
Mohagheghi, Mohammad A.
Iran, Tehran
Tehran University of Medical Sciences
Eshagh Hosseini, Mahmoud
Iran, Tehran
Tehran University of Medical Sciences
Atherton, John Christopher
United Kingdom, Nottingham
University of Nottingham
Statistics
Citations: 423
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1053/j.gastro.2007.06.056
ISSN:
00165085
Research Areas
Cancer
Genetics And Genomics
Study Approach
Quantitative