Antonie van Leeuwenhoek

, Volume 106, Issue 4, pp 637–645 | Cite as

Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree of gastritis in infected Slovenian children

  • Matjaž Homan
  • Anja Šterbenc
  • Boštjan J. Kocjan
  • Boštjan Luzar
  • Nina Zidar
  • Rok Orel
  • Mario Poljak
Original Paper

Abstract

The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9 % of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2,cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.

Keywords

Helicobacter pylori babA2 gene Gastritis Children 

References

  1. Backert S, Clyne M, Tegtmeyer N (2011) Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun Signal 9:28PubMedCentralPubMedCrossRefGoogle Scholar
  2. Boyanova L, Yordanov D, Gergova G, Markovska R, Mitov I (2010) Association of iceA and babA genotypes in Helicobacter pylori strains with patient and strain characteristics. Antonie Van Leeuwenhoek 98:343–350PubMedCrossRefGoogle Scholar
  3. Colbeck JC, Hansen LM, Fong JM, Solnick JV (2006) Genotypic profile of the outer membrane proteins BabA and BabB in clinical isolates of Helicobacter pylori. Infect Immun 74:4375–4378PubMedCentralPubMedCrossRefGoogle Scholar
  4. Delahay RM, Rugge M (2012) Pathogenesis of Helicobacter pylori infection. Helicobacter 17(Suppl 1):9–15PubMedCrossRefGoogle Scholar
  5. Dimitrov G, Gottrand F (2006) Does gastric atrophy exist in children? World J Gastroenterol 12:6274–6279PubMedCentralPubMedGoogle Scholar
  6. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney System. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181PubMedCrossRefGoogle Scholar
  7. Ertem D (2013) Clinical practice: Helicobacter pylori infection in childhood. Eur J Pediatr 172:1427–1434PubMedCrossRefGoogle Scholar
  8. Fujimoto S, Olaniyi Ojo O, Arnqvist A, Wu JY, Odenbreit S, Haas R, Graham DY, Yamaoka Y (2007) Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol 5:49–58PubMedCentralPubMedCrossRefGoogle Scholar
  9. Garcia GT, Aranda KR, Goncalves ME, Cardoso SR, Iriya K, Silva NP, Scaletsky IC (2010) High prevalence of clarithromycin resistance and cagA, vacA, iceA2, and babA2 genotypes of Helicobacter pylori in Brazilian children. J Clin Microbiol 48:4266–4268PubMedCentralPubMedCrossRefGoogle Scholar
  10. Gerhard M, Lehn N, Neumayer N, Borén T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci USA 96:12778–12783PubMedCentralPubMedCrossRefGoogle Scholar
  11. Guarner J, Herrera-Goepfert R, Mohar A, Sanchez L, Halperin D, Ley C, Parsonnet J (2001) Gastric atrophy and extent of intestinal metaplasia in a cohort of Helicobacter pylori- infected patients. Hum Pathol 32:31–35PubMedCrossRefGoogle Scholar
  12. Gwack J, Shin A, Kim CS, Ko KP, Kim Y, Jun JK, Bae J, Park SK, Hong YC, Kang D, Chang SH, Shin HR, Yoo KY (2006) CagA-producing Helicobacter pylori and increased risk of gastric cancer: a nested case–control study in Korea. Br J Cancer 95:639–641PubMedCentralPubMedCrossRefGoogle Scholar
  13. Homan M, Luzar B, Kocjan BJ, Orel R, Mocilnik T, Shrestha M, Kveder M, Poljak M (2009) Prevalence and clinical relevance of cagA, vacA, and iceA genotypes of Helicobacter pylori isolated from Slovenian children. J Pediatr Gastroenterol Nutr 49:289–296PubMedCrossRefGoogle Scholar
  14. Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Borén T (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279:373–377PubMedCrossRefGoogle Scholar
  15. Jang S, Jones KR, Olsen CH, Joo YM, Yoo YJ, Chung IS, Cha JH, Merrell DS (2010) Epidemiological link between gastric disease and polymorphisms in VacA and CagA. J Clin Microbiol 48:559–567PubMedCentralPubMedCrossRefGoogle Scholar
  16. Klindermann A, Lopes AI (2009) Helicobacter pylori infection in pediatrics. Helicobacter 14(Suppl 1):52–57CrossRefGoogle Scholar
  17. Koletzko S, Richy F, Bontems P, Crone J, Kalach N, Monteiro ML, Gottrand F, Celinska-Cedro D, Roma-Giannikou E, Orderda G, Kolacek S, Urruzuno P, Martínez-Gómez MJ, Casswall T, Ashorn M, Bodanszky H, Mégraud F (2006) Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe. Gut 55:1711–1716PubMedCentralPubMedCrossRefGoogle Scholar
  18. Matteo MJ, Armitano RI, Romeo M, Wonaga A, Olmos M, Catalano M (2011) Helicobacter pylori bab genes during chronic colonization. Int J Mol Epidemiol Genet 2:286–291PubMedCentralPubMedGoogle Scholar
  19. Oleastro M, Gerhard M, Lopes AI, Ramalho P, Cabral J, Sousa Guerreiro A, Monteiro L (2003) Helicobacter pylori virulence genotypes in Portuguese children and adults with gastroduodenal pathology. Eur J Clin Microbiol Infect Dis 22:85–91PubMedGoogle Scholar
  20. Oleastro M, Santos A, Cordeiro R, Nunes B, Megraud F, Menard A (2010) Clinical relevance and diversity of two homologous genes encoding glycosyltransferases in Helicobacter pylori. J Clin Microbiol 48:2885–2891PubMedCentralPubMedCrossRefGoogle Scholar
  21. Olfat FO, Zheng Q, Oleastro M, Voland P, Borén T, Karttunen R, Engstrand L, Rad R, Prinz C, Gerhard M (2005) Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol 44:151–156PubMedCrossRefGoogle Scholar
  22. Ozbey G, Dogan Y, Demiroren K (2013) Prevalence of Helicobacter pylori virulence genotypes among children in Eastern Turkey. World J Gastroenterol 19:6585–6589PubMedCentralPubMedCrossRefGoogle Scholar
  23. Pellicano R, Franceschi F, Saracco G, Fagoonee S, Roccarina D, Gasbarrini A (2009) Helicobacters and extragastric diseases. Helicobacter 14(Suppl 1):58–68PubMedCrossRefGoogle Scholar
  24. Platt AR, Woodhall RW, George AL Jr (2007) Improved DNA sequencing quality and efficiency using an optimized fast cycle sequencing protocol. Biotechniques 43:58, 60, 62Google Scholar
  25. Podzorski RP, Podzorski DS, Wuerth A, Tolia V (2003) Analysis of the vacA, cagA, cagE, iceA, and babA2 genes in Helicobacter pylori from sixty-one pediatric patients from the Midwestern United States. Diagn Microbiol Infect Dis 46:83–88PubMedCrossRefGoogle Scholar
  26. Pride DT, Meinersmann RJ, Blaser MJ (2001) Allelic variation within Helicobacter pylori babA and babB. Infect Immun 69:1160–1171PubMedCentralPubMedCrossRefGoogle Scholar
  27. Salama N, Guillemin K, McDaniel TK, Sherlock G, Tompkins L, Falkow S (2000) A whole- genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci USA 97:14668–14673PubMedCentralPubMedCrossRefGoogle Scholar
  28. Sgouros SN, Bergele C (2006) Clinical outcome of patients with Helicobacter pylori infection: the bug, the host, or the environment? Postgrad Med J 82:338–342PubMedCentralPubMedCrossRefGoogle Scholar
  29. Sheu BS, Sheu SM, Yang HB, Huang AH, Wu JJ (2003) Host gastric Lewis expression determines the bacterial density of Helicobacter pylori in babA2 genopositive infection. Gut 52:927–932PubMedCentralPubMedCrossRefGoogle Scholar
  30. Suzuki R, Shiota S, Yamaoka Y (2012) Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori. Infect Genet Evol 12:203–213PubMedCentralPubMedCrossRefGoogle Scholar
  31. Talarico S, Gold BD, Fero J, Thompson DT, Guarner J, Czinn S, Salama NR (2009) Pediatric Helicobacter pylori isolates display distinct gene coding capacities and virulence gene marker profiles. J Clin Microbiol 47:1680–1688PubMedCentralPubMedCrossRefGoogle Scholar
  32. Torres LE, Melián K, Moreno A, Alonso J, Sabatier CA, Hernández M, Bermúdez L, Rodríguez BL (2009) Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World J Gastroenterol 15:204–210PubMedCentralPubMedCrossRefGoogle Scholar
  33. Yamaoka Y (2008) Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis. World J Gastroenterol 14:4265–4272PubMedCentralPubMedCrossRefGoogle Scholar
  34. Yamaoka Y (2010) Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol 7:629–641PubMedCentralPubMedGoogle Scholar
  35. Yamaoka Y (2012) Pathogenesis of Helicobacter pylori-related gastroduodenal diseases from molecular epidemiological studies. Gastroenterol Res Pract 2012:371503PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Matjaž Homan
    • 1
  • Anja Šterbenc
    • 2
  • Boštjan J. Kocjan
    • 2
  • Boštjan Luzar
    • 3
  • Nina Zidar
    • 3
  • Rok Orel
    • 1
  • Mario Poljak
    • 2
  1. 1.Department of Gastroenterology, Hepatology and NutritionUniversity Children’s HospitalLjubljanaSlovenia
  2. 2.Faculty of Medicine, Institute of Microbiology and ImmunologyUniversity of LjubljanaLjubljanaSlovenia
  3. 3.Faculty of Medicine, Institute of PathologyUniversity of LjubljanaLjubljanaSlovenia

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