Skip to main content

Advertisement

SpringerLink
Log in

Association between cagA, vacAi, and dupA genes of Helicobacter pylori and gastroduodenal pathologies in Chilean patients

  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

In addition to the already known cagA gene, novel genetic markers have been associated with Helicobacter pylori (H. pylori) virulence: the dupA and vacAi genes. These genes might play an important role as specific markers to determine the clinical outcome of the disease, especially the vacAi gene, which has been expected to be a good marker of severe pathologies like gastric adenocarcinoma. In the present study, the association of cagA, dupA, and vacAi genes with gastroduodenal pathologies in Chilean patients was studied. One hundred and thirty-two patients positive for H. pylori were divided into two groups—non-severe and severe gastric pathologies—and investigated for the presence of cagA, dupA, and vacAi H. pylori virulence genes by PCR. The cagA gene was detected in 20/132 patients (15.2%), the vacAi1 gene was detected in 54/132 patients (40.9%), the vacAi2 gene was detected in 26/132 patients (19.7%), and the dupA gene was detected in 50/132 (37.9%) patients. Logistic regression model analysis showed that the vacAi1 isoform gene in the infected strains and the severity of the diseases outcome were highly associated, causing severe gastric damage that may lead to gastric cancer (p < 0.0001; OR = 8.75; 95% CI 3.54–21.64). Conversely, cagA (p = 0.3507; OR = 1.62; 95% CI 0.59–4.45) and vacAi2 (p = 0.0114; OR = 3.09; 95% CI 1.26–7.60) genes were not associated with damage, while the dupA gene was associated significantly with non-severe clinical outcome (p = 0.0032; OR = 0.25; 95% CI 0.09–0.65). In addition, dupA gene exerts protection against severe gastric pathologies induced by vacAi1 by delaying the outcome of the disease by approximately 20 years.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Amjad N, Osman HA, Razak N, Kassian J, Din J, Abdullah NB (2010) Clinical significance of Helicobacter pylori cagA and iceA genotype status. World J Gastroenterol 16:4443–4447

    Article  PubMed  PubMed Central  Google Scholar 

  • Arachchi HS, Kalra V, Lal B, Bhatia V, Baba CS, Chakravarthy S, Rohatgi S, Sarma PM, Mishra V, Das B, Ahuja V (2011) Prevalence of duodenal ulcer promoting gene (dupA) of Helicobacter pylori in patients with duodenal ulcer in North Indian population. Helicobacter 12:591–597

    Article  Google Scholar 

  • Chung C, Olivares A, Torres E, Yilmaz O, Cohen H, Perez-Perez G (2010) Diversity of vacA intermediate region among Helicobacter pylori strains from several regions of the world. J Clin Microbiol 48:690–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreccio C, Rollan A, Harris PR, Serrano C, Gederlini A, Margozzini P, Gonzalez C, Aguilera X, Venegas A, Jara A (2007) Gastric cancer is related to early Helicobacter pylori infection in a high-prevalence country. Cancer Epidemiol Biomark Prev 16:662–667

    Article  CAS  Google Scholar 

  • Gomes LI, Rocha GA, Rocha AM, Soares TF, Oliveira CA, Bittencourt PF, Queiroz DM (2008) Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol 20:223–230

    Article  Google Scholar 

  • Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M, Letley DP, Muhammad MK, Argent RH, Atherton JC (2008) Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease. J Clin Microbiol 46:1774–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussein NR, Argent RH, Marx CK, Patel SP, Robinson K, Atherton JC (2010) Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells. J Infect Dis 202:261–269

    Article  CAS  PubMed  Google Scholar 

  • Imagawa S, Ito M, Yoshihara M, Eguchi H, Tanaka S, Chayama K (2010) Helicobacter pylori dupA and gastric acid secretion are negatively associated with gastric cancer development. J Med Microbiol 59:1484–1489

    Article  CAS  PubMed  Google Scholar 

  • Khodaii Z, Ghaderian SM, Akbarzadeh-Najar R, Nejati H, Tabatabaei Panah AS (2011) CagA and vacA status and influence of Helicobacter pylori infection on serum oxidative DNA damage in Iranian patients with peptic ulcer disease. Ir J Med Sci 180:155–161

    Article  CAS  PubMed  Google Scholar 

  • Lu H, Hsu PI, Graham DY, Yamaoka Y (2005) Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterol 128:833–848

    Article  CAS  Google Scholar 

  • Martinez A, Gonzalez C, Kawaguchi F, Montoya R, Corvalan A, Madariaga J, Roa J, García A, Salgado F, Solar H, Palma M (2001) Helicobacter pylori: cagA analysis and vacA genotyping in Chile. Detection of a s2/m1 strain. Rev Med Chil 129:1147–1153

    CAS  PubMed  Google Scholar 

  • Moura SB, Costa RF, Anacleto C, Rocha GA, Rocha AM, Queiroz DM (2012) Single nucleotide polymorphisms of Helicobacter pylori dupA that lead to premature stop codons. Helicobacter 17:176–180

    Article  CAS  PubMed  Google Scholar 

  • Nguyen LT, Uchida T, Tsukamoto Y, Kuroda A, Okimoto T, Kodama M, Murakami K, Fujioka T, Moriyama M (2010) Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population. Clin Microbiol Infect 16:1264–1269

    Article  CAS  PubMed  Google Scholar 

  • O’Ryan ML, Lucero Y, Rabello M, Mamani N, Salinas AM, Peña A, Torres-Torreti JP, Mejías A, Ramilo O, Suarez N, Reynolds HE, Orellana A, Lagomarcino AJ (2015) Persistent and transient Helicobacter pylori infections in early childhood. Clin Infect Dis 61:211–218

    Article  PubMed  Google Scholar 

  • Panayotopoulou EG, Sgouras DN, Papadakos KS, Kalliopi P, Sébastien B, Spyros M, Gerassimos M, George P, Andreas M, Athanasios A (2010) CagA and VacA polymorphisms are associated with distinct pathological features in the Helicobacter pylori infected adults with peptic ulcer and non-peptic ulcer disease. J Clin Microbiol 48:2237–2239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porras C, Nodora J, Ferreccio C, Jimenez S, Dominguez RL, Cook P, Anderson G, Morgan DR, Baker LH, Greenberg ER, Herrero R (2013) Epidemiology of Helicobacter pylori infection in six Latin American countries (SWOG Trial S0701). Cancer Causes Control 24:209–215

    Article  PubMed  Google Scholar 

  • Queiroz DM, Rocha GA, Rocha AM, Moura SB, Saraiva IE, Gomes LI, Soares TF, Melo FF, Cabral MM, Oliveira CA (2011) DupA polymorphisms and risk of Helicobacter pylori-associated diseases. Int J Med Microbiol 301:225–228

    Article  CAS  PubMed  Google Scholar 

  • Rhead J, Letley DP, Marjan-Mohammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC (2007) A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterol 33:926–936

    Article  Google Scholar 

  • Sachs G, Scott DR (2012) Helicobacter pylori: eradication or preservation. F1000 Med Rep 4:1–5

    Google Scholar 

  • Santibáñez M, Aguirre E, Belda S, Aragones N, Saez J, Juan Carlos Rodríguez JC, Galiana A, Sola-Vera J, Ruiz-García M, Paz-Zulueta M, Sarabia-Lavín R, Brotons A, López-Girona E, Pérez E, Sillero C, Royo G (2015) Relationship between tobacco, cagA and vacAi1 virulence factors and bacterial load in patients infected by Helicobacter pylori. PLoS One 10:1–8

    Article  Google Scholar 

  • Sokic-Milutinovic A, Alempijevic T, Milosavljevic T (2015) Role of Helicobacter pylori infection in gastric carcinogenesis: current knowledge and future directions. World J Gastroenterol 21:11654–11672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, De Boer W, Quint W (1998) Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115:58–66

    Article  CAS  PubMed  Google Scholar 

  • Vassallo JA, Barrios E (2008) Actualización ponderada de los factores de riesgo del cáncer. Comisión Honoraria de Lucha Contra el Cáncer, Montevideo, pp 9–119

    Google Scholar 

  • Vega AE, Cortiñas TI, Puig ON, Silva HJ (2010) Molecular characterization and susceptibility testing of Helicobacter pylori strains isolated in western Argentina. Int J Infect Dis 14S:e85–e92

    Article  Google Scholar 

  • Yamaoka Y (2009) Helicobacter pylori typing as a tool for tracking human migration. Clin Microbiol Infect 15:829–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamaoka Y (2012) Pathogenesis of Helicobacter pylori-related gastroduodenal diseases from molecular epidemiological studies. Gastroenterol Res Pract 37:1–9

    Article  Google Scholar 

  • Yordanov D, Boyanova L, Markovska R, Gergova G, Mitov I (2012) Significance of Helicobacter pylori vacA intermediate region genotyping-a Bulgarian study. Diagn Microbiol Infect Dis 74:253–257

    Article  CAS  PubMed  Google Scholar 

  • Zhang KL, Sun Y, Li Y, Liu M, Qu B, Cui SH, Kong QY, Chen XY, Li H, Liu J (2008) Increased frequency of CpG island methylator phenotype and CDH1 methylation in a gastric cancer high-risk region of China. Transl Oncol 1:28–35

  • Zhang RG, Duan GC, Fan QT, Chen SY (2016) Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J Gastrointest Pathophysiol 7:97–107

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This paper was supported by Fondef D03i1105.

Author information

Authors and Affiliations

  1. Laboratory of Bacterial Pathogenesis, Faculty of Biologics Sciences, University of Concepcion, P.O. Box 160-C, Concepcion, Chile

    Esteban Paredes-Osses, Enrique Sanhueza & Apolinaria García Cancino

  2. Department of Statistics, Faculty of Physics and Math’s Sciences, University of Concepcion, Concepcion, Chile

    Katia Sáez

  3. Department of Microbiology, Faculty of Biologics Sciences, University of Concepcion, Concepcion, Chile

    Sonja Hebel & Carlos González

  4. Department of Gastroenterology, Faculty of Medicine, University of Concepcion, Concepcion, Chile

    Carlos Briceño

Authors
  1. Esteban Paredes-Osses
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katia Sáez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enrique Sanhueza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sonja Hebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlos González
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlos Briceño
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Apolinaria García Cancino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Apolinaria García Cancino.

Ethics declarations

The Ethic Committee of the Clinical Hospital “Guillermo Grant Benavente” approved the study protocol (code # 08-03-03). All patients were of first attendance to the hospital and non-previous clinical records were registered. The patients signed an informed consent form prior to acceptance in the study and were additionally asked about antibiotic consumption, previous gastric diseases, smoke inhalation, or alcoholic beverage consumption in order to exclude these factors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paredes-Osses, E., Sáez, K., Sanhueza, E. et al. Association between cagA, vacAi, and dupA genes of Helicobacter pylori and gastroduodenal pathologies in Chilean patients. Folia Microbiol 62, 437–444 (2017). https://doi.org/10.1007/s12223-017-0514-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12223-017-0514-y

Keywords

Search

Navigation