Presence of the Genes cagA, cagE, virB11 and Allelic Variation of vacA of Helicobacter pylori Are Associated with the Activity of Gastritis

Abstract

Non-atrophic active chronic gastritis (ACG) is characterized by the presence of H. pylori in the gastric epithelium, known to be one of the first steps that precede progression to gastric adenocarcinoma. Inactive chronic gastritis (ICG) suggests that the patient has H. pylori gastritis, but this diagnosis is rarely made in routine histopathology. Clinical manifestations associated with H. pylori infection are potentially due to differences in virulence between strains; however, it is unclear if the progression of ACG to ICG depends on the H. pylori strain. The aim of this study was to compare the prevalence of the virulence factors of H. pylori found in patients with ACG and ICG, and its influence on the development of ICG. A significant association was observed between H. pylori detection by histological examination and the activity of gastritis (p < 0.01). Long-term use of proton pump inhibitors (PPI) (>1 year) was reported by 28.6% of the ACG group and 42.5% of the ICG, while no evidence of association between long-term use of PPI and decreased inflammation was found in the patients studied. The genes cagA, cagE and virB11 were statistically associated with ACG (p = 0.01, p < 0.001 and p = 0.002, respectively). In the vacAs1 allele groups, ACG was associated with the most virulent group (p = 0.0015), while ICG was associated with the less virulent group (p < 0.001). The rate of co-infection was significantly higher in ICG than in ACG cases (p = 0.02). In conclusion, this study points to the role of virulent strains of H. pylori in the non-resolution of gastritis.

Share and Cite:

de Negreiros Bessa, P. , Barbosa, F. , do Carmo, A. , Furtado, G. , Barroso, F. and Rabenhosrt, S. (2014) Presence of the Genes cagA, cagE, virB11 and Allelic Variation of vacA of Helicobacter pylori Are Associated with the Activity of Gastritis. Open Journal of Gastroenterology, 4, 347-355. doi: 10.4236/ojgas.2014.411049.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Correa, P. and Houghton, J. (2007) Carcinogenesis of Helicobacter pylori. Gastroenterology, 133, 659-672.
http://dx.doi.org/10.1053/j.gastro.2007.06.026
[2] Oberhuber, G., Püspok, A., Dejaco, C., et al. (1996) Minimal Chronic Inactive Gastritis: Indicator of Pre-Existing Helicobacter pylori Gastritis? Pathology, Research and Practice, 192, 1016-1021.
http://dx.doi.org/10.1016/S0344-0338(96)80043-4
[3] Goldstein, N.S. (2002) Chronic Inactive Gastritis and Coccoid Helicobacter pylori in Patients Treated for Gastroesophageal Reflux Disease or with H. pylori Eradication Therapy. American Journal of Clinical Pathology, 118, 719-726.
http://dx.doi.org/10.1309/LJ4D-E2LX-7UMR-YMTH
[4] Atherton, J.C. (1998) The Clinical Relevance of Strain Types of Helicobacter pylori. Gut, 40, 701-703.
http://dx.doi.org/10.1136/gut.40.6.701
[5] Do Carmo, A.P. and Rabenhorst, S.H. (2011) Importance of vacAs1 Gene in Gastric Cancer Patients Infected with cagA-Negative Helicobacter pylori. APMIS, 7, 485-486.
http://dx.doi.org/10.1111/j.1600-0463.2011.02739.x
[6] Lima, V.P. and Rabenhorst, S.H. (2009) Genes Associados a Virulência do Helicobacter pylori. Revista Brasileira de Cancerologia, 55, 389-396.
[7] Ikenoue, T., Maeda, S., Ogura, K., et al. (2001) Determination of Helicobacter pylori Virulence by Simple Gene Analysis of the Cag Pathogenicity Island. Clinical and Diagnostic Laboratory Immunology, 8, 181-186.
[8] Audibert, C., Burucoa, C., Janvier, B. and Fauchere, J.L. (2001) Implication of the Structure of the Helicobacter pylori Cag Pathogenicity Island in Induction of Interleukin-8 Secretion. Infection and Immunity, 69, 1625-1629.
http://dx.doi.org/10.1128/IAI.69.3.1625-1629.2001
[9] Lima, V.P., De Lima, M.A., Ferreira, M.V., Barros, M.A. and Rabenhorst, S.H. (2010) The Relationship between Helicobacter pylori Genes cagE and virB11 and Gastric Cancer. International Journal of Infectious Diseases, 14, 613-617.
http://dx.doi.org/10.1016/j.ijid.2009.09.006
[10] Ladeira, M.S.P., Bueno, R.C.A., Santos, B.F., Pinto, C.L.S., Prado, R.P., Silveira, M.G., Rodrigues, M.A.M., Bartchewsky, W.J.R., Pedrazzoli, J.J.R., Ribeiro, M.L. and Salvadori, D.M.F. (2008) Relationship among Oxidative DNA Damage, Gastric Mucosal Density and the Relevance of cagA, vacA and iceA Genotypes of Helicobacter pylori. Digestive Diseases and Sciences, 53, 248-255.
http://dx.doi.org/10.1007/s10620-007-9850-0
[11] Sozzi, M., Tomasini, M.L., Vindigni, C., Zanussi, S., Tedeschi, R., Basaglia, G., et al. (2005) Heterogeneity of cag Genotypes and Clinical Outcome of Helicobacter pylori Infection. Journal of Laboratory and Clinical Medicine, 146, 262-270.
http://dx.doi.org/10.1016/j.lab.2005.06.010
[12] Erzin, Y., Koksal, V., Altun, S., Dobrucali, A., Aslan, M., Erdamar, S., Dirican, A. and Kocazeybek, B. (2006) Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA e babA2, Genotypes and Correlation with Clinical Outcome in Turkish Patients with Dyspepsia. Helicobacter, 11, 574-580.
http://dx.doi.org/10.1111/j.1523-5378.2006.00461.x
[13] Yanez, M.A., Barbera, V.M., Soria, E. and Catalan, V. (2009) Quantitative Detection of Helicobacter pylori in Water Samples by Real-Time PCR Amplification of the cag Pathogenicity Island Gene, cagE. Journal of Applied Microbiology, 107, 416-424.
http://dx.doi.org/10.1111/j.1365-2672.2009.04219.x
[14] Foster, G.D. and Tweel, D.J. (1996) Plant Gene Isola-tion: Principles and Practice. John Wiley & Sons, London, 426.
[15] Lage, A.P., Godfroid, E., Fauconnier, A., Burette, A., Butzler, J.P., Bollen, A. and Glupczynski, Y. (1995) Diagnosis of Helicobacter pylori Infection by PCR: Comparison with Other Invasive Techniques and Detection of cagA Gene in Gastric Biopsy Specimens. Journal of Clinical Microbiology, 33, 2752-2756.
[16] Atherton, J.C., Cao, P., Peek, R.M., Tummuru, M.K., Blaser, M.J. and Cover, T.L. (1995) Mosaicism in Vacuolating Cytotoxin Alleles of Helicobacter pylori. Association of Specific vacA Types with Cytotoxin Production and Peptic Ulceration. Journal of Biological Chemistry, 270, 17771-17777.
[17] Domingo, D., Alarcon, T., Pietro, N., Sanchez, I. and Lopez-Brea, M. (1999) cagA and vacA Status of Spanish Helicobacter pylori Clinical Isolates. Journal of Clinical Microbiology, 37, 2113-2114.
[18] El-Zimaity, H.M. (2000) Accurate Diagnosis of Helicobacter pylori with Biopsy. Gastroenterology Clinics of North America, 29, 863-869.
http://dx.doi.org/10.1016/S0889-8553(05)70153-9
[19] Sipponen, P., Oksanen, A., Sarna, S. and Rautelin, H. (2001) Serologic Diagnosis of Helicobacter pylori Infection in Outpatients Aged 45 Years or Less. European Journal of Clinical Microbiology and Infectious Diseases, 20, 554-557.
http://dx.doi.org/10.1007/s100960100547
[20] Malaty, H.M., Graham, D.Y., Logan, N.D. and Ramchatesingh, J. (2001) Helicobacter pylori Infection in Preschool and School Age Minority Children Attending Day Care Centers: Effect of Socioeconomic Indicators and Breast Feeding Practice. Clinical Infectious Diseases, 32, 1387-1392.
http://dx.doi.org/10.1086/320148
[21] Peterson, W.L., Graham, D.Y., Marshall, B., Blaser, M.J., Genta, R.M., Klein, P.D., et al. (1993) Clarithromycin as Monotherapy for Eradication of Helicobacter pylori: A Randomized, Double-Blind Trial. American Journal of Gastroenterology, 88, 1860-1864.
[22] He, Q., Wang, J.P., Osato, M. and Lachman, L.B. (2002) Real-Time Quantitative PCR for Detection of Helicobacter pylori. Journal of Clinical Microbiology, 40, 3720-3728.
http://dx.doi.org/10.1128/JCM.40.10.3720-3728.2002
[23] Gutiérrez, S., Petrola, C., Flores, M., Pinto, A. and Pacheco, M. (2005) Evaluación de la infección por Helicobacter pylori en pacientes VIH positivos mediante ensayos inmunoenzimáticos y amplificación específica de ADN/Evaluation of Infection by Helicobacter pylori in HIV Positive Patients trough Enzyme Immunoassay and Specific Amplification of DNA. Investigación Clínica, 46, 43-52.
[24] Uemura, N. and Okamoto, S. (2000) Effect of Helicobacter pylori Eradication on Subsequent Development of Cancer after Endoscopic Resection of Early Gastric Cancer in Japan. Gastroenterology Clinics of North America, 29, 819-827.
http://dx.doi.org/10.1016/S0889-8553(05)70149-7
[25] Kuipers, E.J., Uyterlinde, A.M., Pena, A.S., Hazenberg, H.J., Bloemena, E., Lindeman, J., et al. (1995) Increase of Helicobacter pylori-Associated Corpus Gastritis during Acid Suppressive Therapy: Implications for Long-Term Safety. American Journal of Gastroenterology, 90, 1401-1406.
[26] Crabtree, J.E., Xiang, Z., Lindley, I.J., Tompkins, D.S., Rappuoli, R. and Covacci, A. (1995) Induction of Interleukin-8 Secretion from Gastric Epithelial Cells by a cagA Negative Isogenic Mutant of Helicobacter pylori. Journal of Clinical Pathology, 48, 967-969.
http://dx.doi.org/10.1136/jcp.48.10.967
[27] Proenca Modena, J.L., Lopes Sales, A.I., Olszanski Acrani, G., Russo, R., Vilela Ribeiro, M.A., Fukuhara, Y., et al. (2007) Association between Helicobacter pylori Genotypes and Gastric Disorders in Relation to the Cag Pathogenicity Island. Diagnostic Microbiology and Infectious Disease, 59, 7-16.
http://dx.doi.org/10.1016/j.diagmicrobio.2007.03.019
[28] Crabtree, J.E. and Lindley, I.J. (1994) Mucosal Interleukin-8 and Helicobacter pylori-Associated Gastroduodenal Disease. European Journal of Gastroenterology & Hepatology, 6, S33-S38.
[29] Boncristiano, M., Paccani, S.R., Barone, S., Ulivieri, C., Patrussi, L., Ilver, D., et al. (2003) The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms. Journal of Experimental Medicine, 198, 1887-1897.
http://dx.doi.org/10.1084/jem.20030621
[30] Molinari, M., Galli, C., De Bernard, M., Norais, N., Ruysschaert, J.M., Rappuoli, R. and Montecucco, C. (1998) The Acid Activation of Helicobacter pylori Toxin VacA: Structural and Membrane Binding Studies. Biochemical and Biophysical Research Communications, 248, 334-340.
http://dx.doi.org/10.1006/bbrc.1998.8808

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.