Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity

Abstract

Objective: To detect the various of H. pylori genotypes, determine the most prevalent one, and to identify the determinants of disease severity. Methods: Biopsies from 90 patients were collected, however 69 were exclusively analyzed. Recognition of H. pylori was made by rapid urease test, histopathology and polymerase chain reaction. The latter was used to amplify genes encoding for virulence markers such as CagA, vacAs1 and vacAs2. Results: cagA was identified in 45 isolates (65.2%), vacAs1 in 54 (78.3%, predominantly vacAs1a), vacAs2 in 15 (21.7%), vacAm1 in 37 (53.6%), vacAm2 in 32 (46.4%), vacAi1 in 36 (52.2%), and vacAi2 in 32 (46.4%) of strains. vacAi1 gene was the only independent marker of pathogenicity. cagA/vacAs1(a)i1m1 was the most prevalent genotype. Conclusion: isolates possess vacAs1(a) as the predominant allelic variant of vacAs types, with a closely equal distributions of m1 and m2 alleles and of i1 and i2 alleles. The majority of the strains from the population studied are of the cagA/vacAs1(a)i1m1 genotype. vacAi1 is the only determinant of disease severity.

Keywords

• H. pylori, vacAs, vacAi, cagA, gastroduodenal disease

Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity

Öz

Amaç: Çeşitli H. pylori genotiplerini saptamak, en yaygın olanı belirlemek ve hastalığın ciddiyetini gösteren belirteçleri saptamakYöntem: Doksan hastadan alınan biyopsiler toplandı ancak bunlardan sadece 69’u analiz edildi. H. pylori tanınması hızlı üreaz testi, histopatoloji ve polimeraz zincir reaksiyonu ile yapıldı. Bu sonuncu aynı zamanda CagA, vacAs1 ve vacAs2 gibi virülans belirteçlerini kodlayan genleri amplifiye etmek için kullanıldı.Bulgular: cagA 45 suşta (% 65,2), vacAs1 54 suşta (% 78,3, ağırlıklı olarak vacAs1a), vacAs2 15 suşta (% 21,7), vacAm1 37 suşta (% 53,6) olarak, vacAm2 32 suşta (% 46,4), vacAi1 36 suşta (% 52,2) ve vacAi2 32 (% 46,4) tespit edildi. vacAi1 geni patojenite ile ilgili tek markerdı. cagA/vacAs1 (a) i1m1 geni en yaygın genotip idi.Sonuç: m1 ve m2 alelleri ve i1 ve i2 alellerinin çok yakın eşit dağılımları ile vacAs tipleri içinde vacAs1(a) genine sahip olan izolatlar en baskın alelik varyant idi. Çalışılan suşların büyük çoğunluğu cagA/vacAs1(a)i1m1 genotipinde idi. Hastalığın ciddiyetini gösteren tek tek belirteç vacAi1 idi

Anahtar Kelimeler

• H. pylori, vacAs, vacAi, cagA, gastroduodenal hastalık

References

1. Fennerty MB. Helicobacter pylori: why it still matters in 2005. Clev Clin J Med 2005; 72 (supp 2):S1-7, S14-21.
2. Arinton G, Samudro P, Soemohardjo S, Sarjadi. Correlation of cagA-positive strains of Helicobacter pylori with topographic distribution and chronic gastritis grading. The Indones J Gas- troenterol Hepatol Digest Endoscopy 2007;8:5-10.
3. Olivares A, Buadze M, Kutubidze T, et al. Prevalence of Heli- cobacter pylori in Georgian patients with dyspepsia. Helico- bacter 2006;11:81-85.
4. Ficher W, Gebert B, Haas R. Novel activities of the Helicobacter pylori vacuolating cytotoxin: from epithelial cells towards the immune system. Int J Med Microbiol 2004; 293:539-547.
5. Rhead JL, Letty DP , Mohammadi M, et al. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroeneterology 2007;133:926-936.
6. Chung C, Olivares A, Torres E, et al. Diversity of vacA interme- diate region among Helicobacter pylori strains from several regions of the world. J Clin Microbiol 2010;48:690-696.
7. Essa AS, Nouh MA, Ghaniam NM, et al. Prevalence of cagA in relation to clinical presentation of Helicobacter pylori infec- tion in Egypt. Scand J Infect Dis 2008;40:730-733.
8. Destura RV, Labio ED, Barrett LJ, et al. Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines. Ann Clin Microbiol Antimicrob 2004;3:25-30.

9. Bancroft G, Gamble A. Theory and practice of histological techniques, 5th edn. London: Churchill Livingston, 2002.
10. Clayton CL, Kleanthous H, Coates PJ, et al. Sensitive detec- tion of Helicobacter pylori by using polymerase chain reac- tion. J Clin Microbiol 1992;30:192-200.
11. Atherton JC, Cao P, Peek RM, et al. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specif- ic vacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995;270:17771-17777.
12. Zhang K, Shan L, Rahman MS, et al. Constitutive and in- ducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 2007;293:375-382.
13. Anderson H, Loivukene K, Sillakivi T, et al. Association of cagA and vacA genotypes of Helicobacter pylori with gastric diseases in Estonia. J Clin Microbiol 2002;40:298-300.
14. Chen XJ, Yan J, Shen YF. Dominant cagA/vacA genotypes and coinfection frequency of Helicobacter pylori in peptic ul- cer or chronic gastritis patients in Zhejiang Province and cor- relations among different genotypes, coinfection and severity of the diseases. Chin Med J Engl 2005;118:460-467
15. Straus EW, Patel H, Chang J, et al. Helicobacter pylori infec- tion and genotyping in patients undergoing upper endoscopy at inner city hospitals. Dig Dis Sci 2002;47:1575-1581.
16. Ghose C, Perez-Perez GI, van Doorn LJ, Domínguez-Bello MG, Blaser MJ. High frequency of gastric colonization with multiple Helicobacter pylori strains in Venezuelan subjects. J Clin Microbiol 2005;43:2635-2641.
17. Saribasak H, Salih BA, Yamaoka Y, Sander E. Analysis of Helicobacter pylori genotypes and correlation with clinical outcome in Turkey. J Clin Microbiol 2004; 42:1648-1651.
18. Khayat AE, Soweid AM, Kattar MM, Tawil A, Gold B and Matar GM. Prevalence and Clinical Relevance of Helico- bacter pylori cagA and vacA genes in Lebanese patients with gastritis and peptic ulcer disease. J Infect Developing Coun- tries 2007;1:55-61.
19. Hussein NR. Helicobacter pylori and gastric cancer in the Middle East: A new enigma? World J Gastroenterol 2010;16:3226–3234.
20. Jafari F, Shokrzadeh L, Dabiri H, et al. vacA genotypes of Helicobacter pylori in relation to cagA status and clinical out- comes in Iranian populations. Jpn J Infet Dis 2008; 61:290- 293.
21. Lin HJ, Perng CL, Lo WC, et al. Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan. World J Gastroenterol 2004;10:2493-2497.
22. Ashour AA, Magalhaes PP, Mendes EN, et al. Distribution of vacA genotypes in Helicobacter pylori strains isolated from Brazilian adult patients with gastritis, duodenal ulcer or gas- tric carcinoma. FEMS Immunol Med Microbiol 2002;33:173- 178.
23. Ahmad T, Sohail K, Rizwan M, et al. Prevalence of Helico- bacter pylori pathogenicity-associated cagA and vacA geno- types among Pakistani dyspeptic patients. FEMS Immunol Med Microbiol 2009;55:34-38.
24. Díaz MI, Valdivia A, Martínez P, et al. Helicobacter pylori va- cAs1a and s1b alleles from clinical isolates from different re- gions of Chile show a distinct geographic distribution. World J Gastroenterol 2005;11:6366-6372.
25. Yakoob J, Abid S, Abbas Z et al. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal dis- eases in Pakistan. BMC Gastroenterology 2009;9:87-94.
26. Han SR, Schreiber HJ, Bhakdi S, et al. vacA genotypes and genetic diversity in clinical isolates of Helicobacter pylori. Clin Diagn Lab Immunol 1998;5:139–145.
27. Nimri LF, Matalka I, Bani Hani K, Ibrahim M. Helicobacter pylori genotypes identified in gastric biopsy specimens from Jordanian patients. BMC Gastroenterol 2006;6:27-32.
28. Sugimoto M, Zali MR, Yamaoka Y. The association of vacA genotypes and Helicobacter pylori- related gastroduodenal diseases in the Middle East. Eur J Clin Microbiol Infect Dis 2009; 28:1227-1236.
29. Jang S, Jones KR, Olsen CH, et al. Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA. J Clin Microbiol 2010;48:559-567.
30. Mohammadi M, Oghalaie A, Mohajerani N, et al. Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mo- saicism as a predictive marker for Iranian dyspeptic patients. Bull Soc Pathol Exot 2003;96:3-5.
31. Terebiznik MR, Raju D, Vázquez CL, et al. Effect of Helico- bacter pylori’s vacuolating cytotoxin on the autophagy path- way in gastric epithelial cells. Autophagy 2009;5:370-379.