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Helicobacter pylori virulence genes in the five largest islands of Indonesia.

Miftahussurur M, Syam AF, Makmun D, Nusi IA, Zein LH - Gut Pathog (2015)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan ; Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia ; Institute of Tropical Disease, Airlangga University, Surabaya, 60115 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 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).

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.

No MeSH data available.


Related in: MedlinePlus

Sequence analysis of CagA structural polymorphisms in Indonesian strains. Eight strains had ABB type; most were Papuan, which was very rare in other countries. Sequences of the first and second segment B in the ABB type were similar to segment B in East-Asian-type-cagA; however, the second segment B contained a trace of the segment D component of East-Asian-type-cagA. The star symbol indicates the sequence similarities among all cagA types. In contrast, the red color emphasizes sequence differences
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Fig1: Sequence analysis of CagA structural polymorphisms in Indonesian strains. Eight strains had ABB type; most were Papuan, which was very rare in other countries. Sequences of the first and second segment B in the ABB type were similar to segment B in East-Asian-type-cagA; however, the second segment B contained a trace of the segment D component of East-Asian-type-cagA. The star symbol indicates the sequence similarities among all cagA types. In contrast, the red color emphasizes sequence differences

Mentions: In total, 43 of 44 strains possessed the cagA gene (97.7 %). Sequence analyses revealed that 23 strains were of the ABD type and 3 were of the AABD type, which were both considered East-Asian-type-cagA (26/43, 60.5 %). Western-type-cagA (ABC, ABCC, BC, B) was found in 20.9 % (9/43) of isolates. One strain with B type was regarded as Western-type-cagA based on the sequence similarity of B-segments with Western-type-cagA. Interestingly, 8 strains had ABB type (18.6 %), which is very rare in other countries. Sequences of both B segments in the ABB type were different from those of East-Asian-type- or Western-type-cagA (Fig. 1). Therefore, we classified the ABB type as an independent group.Fig. 1


Helicobacter pylori virulence genes in the five largest islands of Indonesia.

Miftahussurur M, Syam AF, Makmun D, Nusi IA, Zein LH - Gut Pathog (2015)

Sequence analysis of CagA structural polymorphisms in Indonesian strains. Eight strains had ABB type; most were Papuan, which was very rare in other countries. Sequences of the first and second segment B in the ABB type were similar to segment B in East-Asian-type-cagA; however, the second segment B contained a trace of the segment D component of East-Asian-type-cagA. The star symbol indicates the sequence similarities among all cagA types. In contrast, the red color emphasizes sequence differences
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4594740&req=5

Fig1: Sequence analysis of CagA structural polymorphisms in Indonesian strains. Eight strains had ABB type; most were Papuan, which was very rare in other countries. Sequences of the first and second segment B in the ABB type were similar to segment B in East-Asian-type-cagA; however, the second segment B contained a trace of the segment D component of East-Asian-type-cagA. The star symbol indicates the sequence similarities among all cagA types. In contrast, the red color emphasizes sequence differences
Mentions: In total, 43 of 44 strains possessed the cagA gene (97.7 %). Sequence analyses revealed that 23 strains were of the ABD type and 3 were of the AABD type, which were both considered East-Asian-type-cagA (26/43, 60.5 %). Western-type-cagA (ABC, ABCC, BC, B) was found in 20.9 % (9/43) of isolates. One strain with B type was regarded as Western-type-cagA based on the sequence similarity of B-segments with Western-type-cagA. Interestingly, 8 strains had ABB type (18.6 %), which is very rare in other countries. Sequences of both B segments in the ABB type were different from those of East-Asian-type- or Western-type-cagA (Fig. 1). Therefore, we classified the ABB type as an independent group.Fig. 1

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan ; Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia ; Institute of Tropical Disease, Airlangga University, Surabaya, 60115 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 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).

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.

No MeSH data available.


Related in: MedlinePlus