Clinical–Alimentary TractClinical Relevance of Helicobacter pylori cagA and vacA Gene Polymorphisms
Section snippets
Patients
In this retrospective study, we selected 203 H pylori–infected subjects. A total of 150 patients with benign diseases were selected from a series of 1145 consecutive outpatients admitted to the Endoscopic Unit of the University Hospital of Padova for investigation of dyspepsia. The selection criteria were as follows: (1) presence of H pylori infection (see Supplementary Table 1 for definition; see supplementary material online at www.gastrojournal.org), (2) no previous treatment for H pylori
vacA Typing
Of our 203 samples, 4 and 53 had untypeable vacA s and m regions, respectively. We performed successful vacA i region typing at a later date on DNA from 171 available cases. Typing of 10 cases (1 GC, 4 PU, and 5 gastritis) showed probable mixed strain infection in that both s1 and s2 or both i1 and i2 or both m1 and m2 vacA alleles, or a combination, were found. These cases were not included in subsequent association analyses.
The Polymorphic Structure of vacA
To study the structure of vacA in our samples, we excluded strains
Discussion
The most widely researched and best-established H pylori virulence factors are the vacuolating cytotoxin, VacA, and the cytotoxin-associated protein A, CagA.2, 18, 19, 29 CagA has received renewed interest following the demonstration that the 3′ region of the cagA gene varies in size due to a variable number of repeats encoding type C EPIYA phosphorylation sites.8 For vacA, a new polymorphic region (the i region) has been described and shown to be a major determinant of toxicity; vacA type i1
References (37)
- et al.
Grb2 is a key mediator of Helicobacter pylori CagA protein activities
Mol Cell
(2002) - et al.
Helicobacter pylori CagA protein activates serum response element-driven transcription independently of tyrosine phosphorylation
Gastroenterology
(2002) - et al.
Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori
Gastroenterology
(2004) - et al.
Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA
Gastroenterology
(2006) - et al.
Mosaicism in vacuolating cytotoxin alleles of Helicobacter pyloriAssociation of specific vacA types with cytotoxin production and peptic ulceration
J Biol Chem
(1995) - et al.
Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori
Gastroenterology
(1997) - et al.
Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation
J Biol Chem
(2006) - et al.
A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer
Gastroenterology
(2007) - et al.
Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome
Cytokine
(2005) - et al.
Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH
Gastroenterology
(1999)
Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils
Gastroenterology
Helicobacter pylori and gastrointestinal tract adenocarcinomas
Nat Rev Cancer
CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study
Int J Cancer
Helicobacter pylori persistence: biology and disease
J Clin Invest
Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori
Proc Natl Acad Sci U S A
Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation
Proc Natl Acad Sci U S A
Oncogenic mechanisms of the Helicobacter pylori CagA protein
Nat Rev Cancer
Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells
Proc Natl Acad Sci U S A
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Supported by AIRC regional grant 2005 and by Cancer Research UK and CORE, the digestive diseases charity.
The authors report they have no conflict to disclose.