Skip to main content
Top
Published in: Gut Pathogens 1/2015

Open Access 01-12-2015 | Research

Helicobacter pylori virulence genes in the five largest islands of Indonesia

Authors: Muhammad Miftahussurur, Ari Fahrial Syam, Dadang Makmun, Iswan Abbas Nusi, Lukman Hakim Zein, Zulkhairi, Fardah Akil, Willi Brodus Uswan, David Simanjuntak, Tomohisa Uchida, Pangestu Adi, Amanda Pitarini Utari, Yudith Annisa Ayu Rezkitha, Phawinee Subsomwong, Nasronudin, Yoshio Yamaoka

Published in: Gut Pathogens | Issue 1/2015

Login to get access

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.
Literature
2.
go back to reference Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629–41.PubMedCentralPubMed Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629–41.PubMedCentralPubMed
3.
go back to reference Matsuda M, Shiota S, Matsunari O, Watada M, Murakami K, Fujioka T, Yamaoka Y. Prevalence of two homologous genes encoding glycosyltransferases of Helicobacter pylori in the United States and Japan. J Gastroenterol Hepatol. 2011;26(9):1451–6.PubMedCentralPubMed Matsuda M, Shiota S, Matsunari O, Watada M, Murakami K, Fujioka T, Yamaoka Y. Prevalence of two homologous genes encoding glycosyltransferases of Helicobacter pylori in the United States and Japan. J Gastroenterol Hepatol. 2011;26(9):1451–6.PubMedCentralPubMed
4.
go back to reference Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 2002;99(22):14428–33.PubMedCentralCrossRefPubMed Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 2002;99(22):14428–33.PubMedCentralCrossRefPubMed
5.
go back to reference Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter. 2004;9(5):453–9.CrossRefPubMed Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter. 2004;9(5):453–9.CrossRefPubMed
6.
go back to reference Jones KR, Joo YM, Jang S, Yoo YJ, Lee HS, Chung IS, Olsen CH, Whitmire JM, Merrell DS, Cha JH. Polymorphism in the CagA EPIYA motif impacts development of gastric cancer. J Clin Microbiol. 2009;47(4):959–68.PubMedCentralCrossRefPubMed Jones KR, Joo YM, Jang S, Yoo YJ, Lee HS, Chung IS, Olsen CH, Whitmire JM, Merrell DS, Cha JH. Polymorphism in the CagA EPIYA motif impacts development of gastric cancer. J Clin Microbiol. 2009;47(4):959–68.PubMedCentralCrossRefPubMed
7.
go back to reference Hatakeyama M. Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer. 2004;4(9):688–94.CrossRefPubMed Hatakeyama M. Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer. 2004;4(9):688–94.CrossRefPubMed
8.
go back to reference Uchida T, Nguyen LT, Takayama A, Okimoto T, Kodama M, Murakami K, Matsuhisa T, Trinh TD, Ta L, Ho DQ, et al. Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population. BMC Microbiol. 2009;9:175.PubMedCentralCrossRefPubMed Uchida T, Nguyen LT, Takayama A, Okimoto T, Kodama M, Murakami K, Matsuhisa T, Trinh TD, Ta L, Ho DQ, et al. Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population. BMC Microbiol. 2009;9:175.PubMedCentralCrossRefPubMed
9.
go back to reference Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham D. Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome. Helicobacter. 1998;3(4):241–53.CrossRefPubMed Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham D. Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome. Helicobacter. 1998;3(4):241–53.CrossRefPubMed
10.
go back to reference van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, Quint W. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998;115(1):58–66.CrossRefPubMed van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, Quint W. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998;115(1):58–66.CrossRefPubMed
11.
go back to reference Yamaoka Y, Kikuchi S, el-Zimaity HM, Gutierrez O, Osato MS, Graham DY. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002;123(2):414–24.CrossRefPubMed Yamaoka Y, Kikuchi S, el-Zimaity HM, Gutierrez O, Osato MS, Graham DY. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002;123(2):414–24.CrossRefPubMed
12.
go back to reference Maeda S, Ogura K, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, Omata M. Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut. 1998;42(3):338–43.PubMedCentralCrossRefPubMed Maeda S, Ogura K, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, Omata M. Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut. 1998;42(3):338–43.PubMedCentralCrossRefPubMed
13.
go back to reference Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, Miller GG. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110(6):531–44.PubMed Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, Miller GG. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110(6):531–44.PubMed
14.
go back to reference Xu Q, Morgan RD, Roberts RJ, Xu SY, van Doorn LJ, Donahue JP, Miller GG, Blaser MJ. Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori. Nucleic Acids Res. 2002;30(17):3839–47.PubMedCentralCrossRefPubMed Xu Q, Morgan RD, Roberts RJ, Xu SY, van Doorn LJ, Donahue JP, Miller GG, Blaser MJ. Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori. Nucleic Acids Res. 2002;30(17):3839–47.PubMedCentralCrossRefPubMed
16.
go back to reference Oleastro M, Santos A, Cordeiro R, Nunes B, Megraud F, Menard A. Clinical relevance and diversity of two homologous genes encoding glycosyltransferases in Helicobacter pylori. J Clin Microbiol. 2010;48(8):2885–91.PubMedCentralCrossRefPubMed Oleastro M, Santos A, Cordeiro R, Nunes B, Megraud F, Menard A. Clinical relevance and diversity of two homologous genes encoding glycosyltransferases in Helicobacter pylori. J Clin Microbiol. 2010;48(8):2885–91.PubMedCentralCrossRefPubMed
17.
go back to reference Abdullah AA, Abdullah M, Fauzi A, Syam AF, Simadibrata M, Makmun D. The effectiveness of endoscopic retrograde cholangiopancreatography in the management of patients with jaundice at Cipto Mangunkusumo Hospital, Jakarta. Acta medica Indonesiana. 2012;44(4):298–303.PubMed Abdullah AA, Abdullah M, Fauzi A, Syam AF, Simadibrata M, Makmun D. The effectiveness of endoscopic retrograde cholangiopancreatography in the management of patients with jaundice at Cipto Mangunkusumo Hospital, Jakarta. Acta medica Indonesiana. 2012;44(4):298–303.PubMed
18.
go back to reference Miftahussurur M, Shiota S, Suzuki R, Matsuda M, Uchida T, Kido Y, Kawamoto F, Maimunah U, Adi P, Rezkitha Y, et al. Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests. Epidemiol Infect. 2015;143(5):986–96.CrossRefPubMed Miftahussurur M, Shiota S, Suzuki R, Matsuda M, Uchida T, Kido Y, Kawamoto F, Maimunah U, Adi P, Rezkitha Y, et al. Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests. Epidemiol Infect. 2015;143(5):986–96.CrossRefPubMed
19.
go back to reference Miftahussurur M, Tuda J, Suzuki R, Kido Y, Kawamoto F, Matsuda M, Tantular IS, Pusarawati S, Nasronudin, Harijanto PN, et al. Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: a cross sectional study. Gut pathogens. 2014;6(1):42.PubMedCentralCrossRefPubMed Miftahussurur M, Tuda J, Suzuki R, Kido Y, Kawamoto F, Matsuda M, Tantular IS, Pusarawati S, Nasronudin, Harijanto PN, et al. Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: a cross sectional study. Gut pathogens. 2014;6(1):42.PubMedCentralCrossRefPubMed
20.
go back to reference Xia Y, Yamaoka Y, Zhu Q, Matha I, Gao X. A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. PLoS One. 2009;4(11):e7736.PubMedCentralCrossRefPubMed Xia Y, Yamaoka Y, Zhu Q, Matha I, Gao X. A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. PLoS One. 2009;4(11):e7736.PubMedCentralCrossRefPubMed
21.
go back to reference Matsunari O, Shiota S, Suzuki R, Watada M, Kinjo N, Murakami K, Fujioka T, Kinjo F, Yamaoka Y. Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan. J Clin Microbiol. 2012;50(3):876–83.PubMedCentralCrossRefPubMed Matsunari O, Shiota S, Suzuki R, Watada M, Kinjo N, Murakami K, Fujioka T, Kinjo F, Yamaoka Y. Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan. J Clin Microbiol. 2012;50(3):876–83.PubMedCentralCrossRefPubMed
22.
go back to reference Takahashi A, Shiota S, Matsunari O, Watada M, Suzuki R, Nakachi S, Kinjo N, Kinjo F, Yamaoka Y. Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan. Helicobacter. 2013;18(1):66–72.CrossRefPubMed Takahashi A, Shiota S, Matsunari O, Watada M, Suzuki R, Nakachi S, Kinjo N, Kinjo F, Yamaoka Y. Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan. Helicobacter. 2013;18(1):66–72.CrossRefPubMed
23.
go back to reference Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter. 2004;9(5):453–9.CrossRefPubMed Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter. 2004;9(5):453–9.CrossRefPubMed
24.
go back to reference Yamaoka Y, Kato M, Asaka M. Geographic differences in gastric cancer incidence can be explained by differences between Helicobacter pylori strains. Intern Med. 2008;47(12):1077–83.PubMedCentralCrossRefPubMed Yamaoka Y, Kato M, Asaka M. Geographic differences in gastric cancer incidence can be explained by differences between Helicobacter pylori strains. Intern Med. 2008;47(12):1077–83.PubMedCentralCrossRefPubMed
25.
go back to reference Utsumi T, Lusida MI, Yano Y, Nugrahaputra VE, Amin M, Juniastuti, Soetjipto, Hayashi Y, Hotta H. Complete genome sequence and phylogenetic relatedness of hepatitis B virus isolates in Papua, Indonesia. J Clin Microbiol. 2009;47(6):1842–7.PubMedCentralCrossRefPubMed Utsumi T, Lusida MI, Yano Y, Nugrahaputra VE, Amin M, Juniastuti, Soetjipto, Hayashi Y, Hotta H. Complete genome sequence and phylogenetic relatedness of hepatitis B virus isolates in Papua, Indonesia. J Clin Microbiol. 2009;47(6):1842–7.PubMedCentralCrossRefPubMed
26.
go back to reference Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, Suerbaum S, Achtman M, Linz B. A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet. 2010;6(8):e1001069.PubMedCentralCrossRefPubMed Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, Suerbaum S, Achtman M, Linz B. A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet. 2010;6(8):e1001069.PubMedCentralCrossRefPubMed
27.
go back to reference Zhang XS, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H, Backert S, Blaser MJ. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions. PLoS Pathog. 2015;11(2):e1004621.PubMedCentralCrossRefPubMed Zhang XS, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H, Backert S, Blaser MJ. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions. PLoS Pathog. 2015;11(2):e1004621.PubMedCentralCrossRefPubMed
28.
go back to reference Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N. Engl J Med. 2001;345(11):784–9.CrossRefPubMed Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N. Engl J Med. 2001;345(11):784–9.CrossRefPubMed
29.
go back to reference Hansson LE, Nyren O, Hsing AW, Bergstrom R, Josefsson S, Chow WH, Fraumeni JF Jr, Adami HO. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N. Engl J Med. 1996;335(4):242–9.CrossRefPubMed Hansson LE, Nyren O, Hsing AW, Bergstrom R, Josefsson S, Chow WH, Fraumeni JF Jr, Adami HO. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N. Engl J Med. 1996;335(4):242–9.CrossRefPubMed
30.
go back to reference Chomvarin C, Namwat W, Chaicumpar K, Mairiang P, Sangchan A, Sripa B, Tor-Udom S, Vilaichone RK. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis. 2008;12(1):30–6.CrossRefPubMed Chomvarin C, Namwat W, Chaicumpar K, Mairiang P, Sangchan A, Sripa B, Tor-Udom S, Vilaichone RK. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis. 2008;12(1):30–6.CrossRefPubMed
31.
go back to reference Rahman M, Mukhopadhyay AK, Nahar S, Datta S, Ahmad MM, Sarker S, Masud IM, Engstrand L, Albert MJ, Nair GB, et al. DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh. J Clin Microbiol. 2003;41(5):2008–14.PubMedCentralCrossRefPubMed Rahman M, Mukhopadhyay AK, Nahar S, Datta S, Ahmad MM, Sarker S, Masud IM, Engstrand L, Albert MJ, Nair GB, et al. DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh. J Clin Microbiol. 2003;41(5):2008–14.PubMedCentralCrossRefPubMed
33.
go back to reference Heneghan MA, McCarthy CF, Moran AP. Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host lewis phenotype and inflammatory response. Infect Immun. 2000;68(2):937–41.PubMedCentralCrossRefPubMed Heneghan MA, McCarthy CF, Moran AP. Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host lewis phenotype and inflammatory response. Infect Immun. 2000;68(2):937–41.PubMedCentralCrossRefPubMed
34.
go back to reference Schmidt HM, Andres S, Kaakoush NO, Engstrand L, Eriksson L, Goh KL, Fock KM, Hilmi I, Dhamodaran S, Forman D, et al. The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: a case-control study. Gut pathogens. 2009;1(1):5.PubMedCentralCrossRefPubMed Schmidt HM, Andres S, Kaakoush NO, Engstrand L, Eriksson L, Goh KL, Fock KM, Hilmi I, Dhamodaran S, Forman D, et al. The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: a case-control study. Gut pathogens. 2009;1(1):5.PubMedCentralCrossRefPubMed
35.
go back to reference Shiota S, Watada M, Matsunari O, Iwatani S, Suzuki R, Yamaoka Y. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLoS One. 2012;7(1):e30354.PubMedCentralCrossRefPubMed Shiota S, Watada M, Matsunari O, Iwatani S, Suzuki R, Yamaoka Y. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLoS One. 2012;7(1):e30354.PubMedCentralCrossRefPubMed
36.
go back to reference Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, et al. Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut. 2012;61(5):646–64.CrossRefPubMed Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, et al. Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut. 2012;61(5):646–64.CrossRefPubMed
37.
go back to reference Shiota S, Suzuki R, Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J Dig Dis 2013. Shiota S, Suzuki R, Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J Dig Dis 2013.
38.
go back to reference Dixon M, Genta R, Yardley J, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161–81.CrossRefPubMed Dixon M, Genta R, Yardley J, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161–81.CrossRefPubMed
39.
go back to reference Bornschein J, Selgrad M, Wex T, Kuester D, Malfertheiner P. Serological assessment of gastric mucosal atrophy in gastric cancer. BMC Gastroenterol. 2012;12:10.PubMedCentralCrossRefPubMed Bornschein J, Selgrad M, Wex T, Kuester D, Malfertheiner P. Serological assessment of gastric mucosal atrophy in gastric cancer. BMC Gastroenterol. 2012;12:10.PubMedCentralCrossRefPubMed
40.
go back to reference Uchida T, Kanada R, Tsukamoto Y, Hijiya N, Matsuura K, Yano S, Yokoyama S, Kishida T, Kodama M, Murakami K, et al. Immunohistochemical diagnosis of the cagA-gene genotype of Helicobacter pylori with anti-East Asian CagA-specific antibody. Cancer Sci. 2007;98(4):521–8.CrossRefPubMed Uchida T, Kanada R, Tsukamoto Y, Hijiya N, Matsuura K, Yano S, Yokoyama S, Kishida T, Kodama M, Murakami K, et al. Immunohistochemical diagnosis of the cagA-gene genotype of Helicobacter pylori with anti-East Asian CagA-specific antibody. Cancer Sci. 2007;98(4):521–8.CrossRefPubMed
41.
go back to reference Yamaoka Y, Kikuchi S, el-Zimaity H, Gutierrez O, Osato M, Graham D. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002;123(2):414–24.CrossRefPubMed Yamaoka Y, Kikuchi S, el-Zimaity H, Gutierrez O, Osato M, Graham D. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002;123(2):414–24.CrossRefPubMed
42.
go back to reference Oleastro M, Monteiro L, Lehours P, Mégraud F, Ménard A. Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization. Infect Immun. 2006;74(7):4064–74.PubMedCentralCrossRefPubMed Oleastro M, Monteiro L, Lehours P, Mégraud F, Ménard A. Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization. Infect Immun. 2006;74(7):4064–74.PubMedCentralCrossRefPubMed
43.
go back to reference Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270(30):17771–7.CrossRefPubMed Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270(30):17771–7.CrossRefPubMed
44.
go back to reference Yamaoka Y, El-Zimaity H, Gutierrez O, Figura N, Kim J, Kodama T, Kashima K, Graham D, Kim J. Relationship between the cagA 3’ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999;117(2):342–9.CrossRefPubMed Yamaoka Y, El-Zimaity H, Gutierrez O, Figura N, Kim J, Kodama T, Kashima K, Graham D, Kim J. Relationship between the cagA 3’ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999;117(2):342–9.CrossRefPubMed
45.
go back to reference Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY. Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol. 1999;37(7):2274–9.PubMedCentralPubMed Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY. Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol. 1999;37(7):2274–9.PubMedCentralPubMed
Metadata
Title
Helicobacter pylori virulence genes in the five largest islands of Indonesia
Authors
Muhammad Miftahussurur
Ari Fahrial Syam
Dadang Makmun
Iswan Abbas Nusi
Lukman Hakim Zein
Zulkhairi
Fardah Akil
Willi Brodus Uswan
David Simanjuntak
Tomohisa Uchida
Pangestu Adi
Amanda Pitarini Utari
Yudith Annisa Ayu Rezkitha
Phawinee Subsomwong
Nasronudin
Yoshio Yamaoka
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2015
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-015-0072-2

Other articles of this Issue 1/2015

Gut Pathogens 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine