Abstract
The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The best known genotypic virulence factors of H. pylori are cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA). The objective of this study was to assess the relationship between H. pylori cagA and vacA status and histopathological findings. Esophagogastrodoedonoscopy was performed in 80 dyspeptic patients. Antrum and corpus biopsies were obtained for isolation of H. pylori and for histopathological assessment. The polymerase chain reaction was used to detect cagA and vacA genes of H. pylori using specific primers. Biopsy samples were stained with hematoxylin and eosin, and histopathological findings were graded using the “updated Sydney system”. H. pylori from 57 of the 80 patients was incubated. Of the 57 patients, 44 were cagA positive. In the corpus biopsy specimens there was a significant relationship between the density of H. pylori colonization (P = 0.02) and chronic inflammation (P = 0.02) and cagA-positive genotypes. In the antrum specimens there was a significant relationship between cagA positivity and neutrophil activity (P = 0.003) and glandular atrophy (P = 0.002), but not with H. pylori density, chronic inflammation, and intestinal metaplasia. The odds ratio of cagA-positive vs. cagA-negative strains for the presence of glandular atrophy, irrespective of grading and of gastric localization, was 4.62 (95% CI, 1.18–18.08, P = 0.041). No significant relationships were observed between vacA s1 and s2 genotypes and histopathological parameters. Corpus neutrophil infiltration was found to be more severe in the m1 group than in the m2 group (P = 0.004). Other histopathological features showed no difference between m1 and m2 genotypes. In conclusion H. pylori strains showing cagA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.
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References
Dunn BE, Cohen H, Blaser MJ (1997) Helicobacter pylori. Clin Microbiol Rev 10:720–741
Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD (1994) Helicobacter pylori infection and gastric lymphoma. N Engl J Med 330:1267–1271. doi:10.1056/NEJM199405053301803
Israel DA, Peek RM (2001) Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther 15:1271–1290. doi:10.1046/j.1365-2036.2001.01052.x
McGee DJ, Mobley HLT (2000) Pathogenesis of Helicobacter pylori infection. Curr Opin Gastroenterol 16:24–31. doi:10.1097/00001574-200001000-00005
Jenks PJ, Megraud F, Labigne A (1998) Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the cag pathogenicity island. Gut 43:752–758
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. doi:10.1016/S0016-5085(98)70365-8
Yamaoka Y, Souchek J, Odenbreit S, Haas R, Arnqvist A, Boren T, Kodama T, Osato MS, Gutierrez O, Kim JG, Graham DY (2002) Discrimination between cases of duodenal ulcer and gastritis on the basis of putative virulence factors of Helicobacter pylori. J Clin Microbiol 40:2244–2246. doi:10.1128/JCM.40.6.2244-2246.2002
Palli D, Menegatti M, Masala G, Ricci C, Saieva C, Holton J, Gatta L, Miglioli M, Vaira D (2002) Helicobacter pylori infection, anti-cagA antibodies and peptic ulcer: a case-control study in Italy. Aliment Pharmacol Ther 16:1015–1020. doi:10.1046/j.1365-2036.2002.01253.x
Aydin F, Kaklikkaya N, Ozgur O, Cubukcu K, Kilic AO, Tosun I, Erturk M (2004) Distribution of vacA alleles and cagA status of Helicobacter pylori in peptic ulcer disease and non-ulcer dyspepsia. Clin Microbiol Infect 10:1102–1104. doi:10.1111/j.1469-0691.2004.00989.x
Sezikli M, Guliter S, Apan TZ, Aksoy A, Keles H, Ozkurt ZN (2006) Frequencies of serum antibodies to Helicobacter pylori CagA and VacA in a Turkish population with various gastroduodenal diseases. Int J Clin Pract 60:1239–1243. doi:10.1111/j.1742-1241.2005.00778.x
Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, Sato F, Kato T, Kohli Y, Kuriyama M (1997) Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 35:1710–1714
van Doorn LJ, Figueiredo C, Sanna R, Pena S, Midolo P, Ng EK, Atherton JC, Blaser MJ, Quint WG (1998) Expanding allelic diversity of Helicobacter pylori vacA. J Clin Microbiol 36:2597–2603
Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270:17771–17777. doi:10.1074/jbc.270.30.17771
Pagliaccia C, de Bernard M, Lupetti P, Ji X, Burroni D, Cover TL, Papini E, Rappuoli R, Telford JL, Reyrat JM (1998) The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci USA 95:10212–10217. doi:10.1073/pnas.95.17.10212
Maeda S, Ogura K, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, Omata M (1998) Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut 42:338–343
Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY (1998) Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome. Helicobacter 3:241–253. doi:10.1046/j.1523-5378.1998.08056.x
Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Dirican A, Kocazeybek B (2006) Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes, and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 11:574–580. doi:10.1111/j.1523-5378.2006.00461.x
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 20:1161–1181
Spencer J, Wotherspoon AC (1997) Gastric MALT lymphoma and Helicobacter pylori. Cancer Surv 30:213–231
Graham DY (2000) Helicobacter pylori infection is the primary cause of gastric cancer. J Gastroenterol 35(Suppl 12):90–97
Demirturk L, Ozel AM, Yazgan Y, Solmazgul E, Yildirim S, Gultepe M, Gurbuz AK (2001) CagA status in dyspeptic patients with and without peptic ulcer disease in Turkey: association with histopathologic findings. Helicobacter 6:163–168. doi:10.1046/j.1523-5378.2001.00024.x
Bulent K, Murat A, Esin A, Fatih K, MMMurat H, Hakan H, Melih K, Mehmet A, Bulent Y, Fatih H (2003) Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population. World J Gastroenterol 9:1580–1583
Saruc M, Demir MA, Kucukmetin N, Kandiloglu AR, Akarca US, Yuceyar H (2002) Histological and clinical predictive value of determination of tissue CagA status by PCR in Helicobacter pylori infected patients; results of the large population based study in western Turkey. Hepatogastroenterology 49:878–881
Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ (2007) Current concepts in the management of Helicobacter pylori infection: the Maastricht III consensus report. Gut 56:772–781. doi:10.1136/gut.2006.101634
Malfertheiner P, Megraud F, O’Morain C, Hungin AP, Jones R, Axon A, Graham DY, Tytgat G (2002) Current concepts in the management of Helicobacter pylori infection–the Maastricht 2–2000 consensus report. Aliment Pharmacol Ther 16:167–180. doi:10.1046/j.1365-2036.2002.01169.x
Beales IL, Crabtree JE, Scunes D, Covacci A, Calam J (1996) Antibodies to CagA protein are associated with gastric atrophy in Helicobacter pylori infection. Eur J Gastroenterol Hepatol 8:645–649
Warburton VJ, Everett S, Mapstone NP, Axon AT, Hawkey P, Dixon MF (1998) Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis. J Clin Pathol 51:55–61
Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112:92–99. doi:10.1016/S0016-5085(97)70223-3
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This study was supported financially by the Trakya University Scientific Research Fund (TUBAP-594) and has received a grant from the United European Gastroenterology Federation in the 13th UEGW, Copenhagen, Denmark, 2005.
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Umit, H., Tezel, A., Bukavaz, S. et al. The Relationship Between Virulence Factors of Helicobacter pylori and Severity of Gastritis in Infected Patients. Dig Dis Sci 54, 103–110 (2009). https://doi.org/10.1007/s10620-008-0316-9
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DOI: https://doi.org/10.1007/s10620-008-0316-9