Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms.
OBJECTIVE
The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease.


METHODS
We studied 203 H pylori-infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction.


RESULTS
cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98-27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41-125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19-5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained.


CONCLUSIONS
We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA.
Basso
Daniela
D
Department of Laboratory Medicine, University of Padova, Padova, Italy. biolmol@unipd.it
Zambon
Carlo-Federico
CF
Letley
Darren P
DP
Stranges
Alessia
A
Marchet
Alberto
A
Rhead
Joanne L
JL
Schiavon
Stefania
S
Guariso
Graziella
G
Ceroti
Marco
M
Nitti
Donato
D
Rugge
Massimo
M
Plebani
Mario
M
Atherton
John C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D005756:Gastritis / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology; D005838:Genotype; D016481:Helicobacter Infections / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010437:Peptic Ulcer / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D013270:Stomach / Q000382:microbiology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori