Helicobacter pylori virulence genes in the five largest islands of Indonesia

Abstract
Background: It 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.
Methods: The 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.
Results: A 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 Pap-
uan. 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 posi-
tive 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).
Conclusions: In 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.