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Published in: Gut Pathogens 1/2009

Open Access 01-12-2009 | Research

Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA

Authors: Monica Oleastro, Rita Cordeiro, Yoshio Yamaoka, Dulciene Queiroz, Francis Mégraud, Lurdes Monteiro, Armelle Ménard

Published in: Gut Pathogens | Issue 1/2009

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Abstract

Background

homB encodes a Helicobacter pylori outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD) and was shown to induce activation of interleukin-8 secretion in vitro, as well as contributing to bacterial adherence. Its 90%-similar gene, homA, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with homB and homA, as well as with the H. pylori virulence factors cagA, babA and vacA, in 415 H. pylori strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated.

Results

Both homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD), homB, cagA and vacA s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively), and homA was closely correlated with NUD (p = 0.072). In East Asian strains (n = 138, 73 PUD and 65 NUD), homB was found more frequently than homA, and none of these genes was associated with the clinical outcome.
Overall, homB was associated with the presence of cagA (p = 0.043) and vacA s1 (p < 0.001), whereas homA was found more frequently in cagA-negative (p = 0.062) and vacA s2 (p < 0.001) strains.
Polymorphisms in homB and homA copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the homB two-copy genotype and PUD was also observed, emphasizing the role of homB in the virulence of the strain.

Conclusion

The global results suggest that homB and homA contribute to the determination of clinical outcome.
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Literature
1.
go back to reference NIH Consensus Development Panel: Helicobacter pylori in peptic ulcer disease. JAMA, ed. NIH Consensus Development Panel on Helicobacter pylori in peptic ulcer disease. 1994, 65-9. NIH Consensus Development Panel: Helicobacter pylori in peptic ulcer disease. JAMA, ed. NIH Consensus Development Panel on Helicobacter pylori in peptic ulcer disease. 1994, 65-9.
2.
go back to reference Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK: Helicobacter pylori infection and the risk of gastric carcinoma. N Eng J Med. 1991, 325: 1127-31.CrossRef Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK: Helicobacter pylori infection and the risk of gastric carcinoma. N Eng J Med. 1991, 325: 1127-31.CrossRef
3.
go back to reference Stolte M, Bayerdörffer E, Morgner A, Alpen B, Wündisch T, Thiede C, Neubauer A: Helicobacter and gastric MALT lymphoma. Gut. 2002, 50 (Suppl 3): 19-24. Stolte M, Bayerdörffer E, Morgner A, Alpen B, Wündisch T, Thiede C, Neubauer A: Helicobacter and gastric MALT lymphoma. Gut. 2002, 50 (Suppl 3): 19-24.
4.
go back to reference Ilver D, Arnqvist A, Ögren J, Frick I-M, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T: Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998, 279: 373-7. 10.1126/science.279.5349.373.CrossRefPubMed Ilver D, Arnqvist A, Ögren J, Frick I-M, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T: Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998, 279: 373-7. 10.1126/science.279.5349.373.CrossRefPubMed
5.
go back to reference Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraia S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarstrom L, Boren T: Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science. 2002, 297: 573-8. 10.1126/science.1069076.PubMedCentralCrossRefPubMed Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraia S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarstrom L, Boren T: Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science. 2002, 297: 573-8. 10.1126/science.1069076.PubMedCentralCrossRefPubMed
6.
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): 414-424. 10.1053/gast.2002.34781.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): 414-424. 10.1053/gast.2002.34781.CrossRefPubMed
7.
go back to reference Oleastro M, Cordeiro R, Ferrand J, Nunes B, Lehours P, Carvalho-Oliveira I, Mendes AI, Penque D, Monteiro L, Megraud F, Menard A: Evaluation of the clinical significance of hom B, a novel candidate marker of Helicobacter pylori strains associated with peptic ulcer disease. J Infect Dis. 2008, 198: 1379-87. 10.1086/592166.CrossRefPubMed Oleastro M, Cordeiro R, Ferrand J, Nunes B, Lehours P, Carvalho-Oliveira I, Mendes AI, Penque D, Monteiro L, Megraud F, Menard A: Evaluation of the clinical significance of hom B, a novel candidate marker of Helicobacter pylori strains associated with peptic ulcer disease. J Infect Dis. 2008, 198: 1379-87. 10.1086/592166.CrossRefPubMed
8.
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: 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: 338-43.PubMedCentralCrossRefPubMed
9.
go back to reference Mizushima T, Sugiyama T, Komatsu Y, Ishizuka J, Kato M, Asaka M: Clinical relevance of the babA2 genotype of Helicobacter pylori in Japanese clinical isolates. J Clin Microbiol. 2001, 39: 2463-5. 10.1128/JCM.39.7.2463-2465.2001.PubMedCentralCrossRefPubMed Mizushima T, Sugiyama T, Komatsu Y, Ishizuka J, Kato M, Asaka M: Clinical relevance of the babA2 genotype of Helicobacter pylori in Japanese clinical isolates. J Clin Microbiol. 2001, 39: 2463-5. 10.1128/JCM.39.7.2463-2465.2001.PubMedCentralCrossRefPubMed
10.
go back to reference Tsugane S: Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence. Cancer Sci. 2005, 96: 1-6.CrossRefPubMed Tsugane S: Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence. Cancer Sci. 2005, 96: 1-6.CrossRefPubMed
11.
go back to reference Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ: Comparative genomics of Helicobacter pylori: Analysis of the outer membrane protein families. Infect Immun. 2000, 68: 4155-68. 10.1128/IAI.68.7.4155-4168.2000.PubMedCentralCrossRefPubMed Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ: Comparative genomics of Helicobacter pylori: Analysis of the outer membrane protein families. Infect Immun. 2000, 68: 4155-68. 10.1128/IAI.68.7.4155-4168.2000.PubMedCentralCrossRefPubMed
12.
go back to reference Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M: Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA. 2004, 101: 2106-11. 10.1073/pnas.0308573100.PubMedCentralCrossRefPubMed Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M: Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA. 2004, 101: 2106-11. 10.1073/pnas.0308573100.PubMedCentralCrossRefPubMed
13.
go back to reference Pride DT, Meinersmann RJ, Blaser MJ: Allelic variation within Helicobacter pylori babA and babB. Infect Immun. 2001, 69: 1160-71. 10.1128/IAI.69.2.1160-1171.2001.PubMedCentralCrossRefPubMed Pride DT, Meinersmann RJ, Blaser MJ: Allelic variation within Helicobacter pylori babA and babB. Infect Immun. 2001, 69: 1160-71. 10.1128/IAI.69.2.1160-1171.2001.PubMedCentralCrossRefPubMed
14.
15.
go back to reference Peck B, Ortkamp M, Diehl KD, Hundt E, Knapp B: Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. Nucl Acids Res. 1999, 27: 3325-33. 10.1093/nar/27.16.3325.PubMedCentralCrossRefPubMed Peck B, Ortkamp M, Diehl KD, Hundt E, Knapp B: Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. Nucl Acids Res. 1999, 27: 3325-33. 10.1093/nar/27.16.3325.PubMedCentralCrossRefPubMed
16.
go back to reference Gerhard M, Lehn N, Neumayer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C: Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci USA. 1999, 96: 12778-83. 10.1073/pnas.96.22.12778.PubMedCentralCrossRefPubMed Gerhard M, Lehn N, Neumayer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C: Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci USA. 1999, 96: 12778-83. 10.1073/pnas.96.22.12778.PubMedCentralCrossRefPubMed
17.
go back to reference Olfat FO, Zheng Q, Oleastro M, Voland P, Boren T, Karttunen R, Engstrand L, Rad R, Prinz C, Gerhard M: Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol. 2005, 44: 151-6. 10.1016/j.femsim.2004.10.010.CrossRefPubMed Olfat FO, Zheng Q, Oleastro M, Voland P, Boren T, Karttunen R, Engstrand L, Rad R, Prinz C, Gerhard M: Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol. 2005, 44: 151-6. 10.1016/j.femsim.2004.10.010.CrossRefPubMed
18.
go back to reference Oliveira AG, Santos A, Guerra JB, Rocha GG, Rocha AMC, Oliveira CA, Cabral M, Nogueira A, Queiroz DMM: babA 2- and cag A-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol. 2003, 41: 3964-6. 10.1128/JCM.41.8.3964-3966.2003.PubMedCentralCrossRefPubMed Oliveira AG, Santos A, Guerra JB, Rocha GG, Rocha AMC, Oliveira CA, Cabral M, Nogueira A, Queiroz DMM: babA 2- and cag A-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol. 2003, 41: 3964-6. 10.1128/JCM.41.8.3964-3966.2003.PubMedCentralCrossRefPubMed
19.
go back to reference Oleastro M, Monteiro L, Lehours P, Megraud F, Menard A: Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization. Infect Immun. 2006, 74: 4064-74. 10.1128/IAI.00123-06.PubMedCentralCrossRefPubMed Oleastro M, Monteiro L, Lehours P, Megraud F, Menard A: Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization. Infect Immun. 2006, 74: 4064-74. 10.1128/IAI.00123-06.PubMedCentralCrossRefPubMed
20.
go back to reference Atherton JC, Cao P, Peek RM, Tummuru MKR, Blaser MJ, Cover TL: Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori – Association of specific vac A types with cytotoxin production and peptic ulceration. J Biol Chem. 1995, 270: 17771-7. 10.1074/jbc.270.30.17771.CrossRefPubMed Atherton JC, Cao P, Peek RM, Tummuru MKR, Blaser MJ, Cover TL: Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori – Association of specific vac A types with cytotoxin production and peptic ulceration. J Biol Chem. 1995, 270: 17771-7. 10.1074/jbc.270.30.17771.CrossRefPubMed
21.
go back to reference Tummuru MKR, Cover TL, Blaser MJ: Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993, 61: 1799-809.PubMedCentralPubMed Tummuru MKR, Cover TL, Blaser MJ: Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993, 61: 1799-809.PubMedCentralPubMed
Metadata
Title
Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA
Authors
Monica Oleastro
Rita Cordeiro
Yoshio Yamaoka
Dulciene Queiroz
Francis Mégraud
Lurdes Monteiro
Armelle Ménard
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2009
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/1757-4749-1-12

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