Abstract

BackgroundIt remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors.MethodsThe genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system.ResultsA total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/β-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/β-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/β-(1,3)galT type among different ethnic groups (P < 0.05).ConclusionsIn addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/β-(1,3)galT double positive genotype.

Highlights

  • IntroductionIt remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is related to low Helicobacter pylori pathogenicity

  • It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or owing to low H. pylori pathogenicity

  • We found that subjects infected with strains with EPIYT sequences had higher activity and inflammation scores in the antrum than those with EPIYA sequences, which is consistent with the association between EPIYT sequences and duodenal ulcer (DU)

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Summary

Introduction

It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is related to low Helicobacter pylori pathogenicity. The sequence of the second repeat region was found to differ considerably between East-Asian-type-cagA and Westerntype-cagA. The pre-EPIYA region of cagA, located about 300-bp upstream of the first EPIYA motif, has been investigated. Alignment of these sequences revealed that a 39-bp deletion was present in most strains isolated from East Asia, but was absent in most strains from Western countries (no deletion) [8]

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