J Korean Med Sci.  2012 Feb;27(2):190-193. 10.3346/jkms.2012.27.2.190.

Relationship between Helicobacter pylori Virulence Genes and Clinical Outcomes in Saudi Patients

Affiliations
  • 1College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia. mmarie@ksu.edu.sa

Abstract

Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA s- and m- region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacA s1/m2 genotype and gastritis cases, and a significant correlation between vacA s1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacA s1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene.

Keyword

Helicobacter pylori; cagA; vacA; Gastritis; Peptic Ulcer

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Antigens, Bacterial/*genetics
Bacterial Proteins/*genetics
DNA, Bacterial/genetics
Female
Gastritis/genetics/microbiology/pathology
Genotype
Helicobacter Infections/*epidemiology/*microbiology/pathology
Helicobacter pylori/*genetics/isolation & purification
Humans
Male
Middle Aged
Peptic Ulcer/genetics/microbiology/pathology
Polymerase Chain Reaction
Saudi Arabia
Virulence Factors/genetics
Young Adult

Figure

  • Fig. 1 PCR genotyping of vacA and cagA status from different cases. Primers described in Table 1 were used for PCR reaction (Lanes- 1 = molecular weight marker; 2 = cagA+; 3 = m1; 4 = m2; 5 = s1a; 6 = s1b; 7 = s2 and 8 = Negative control [without DNA]).


Reference

1. Marshall BJ. Helicobacter pylori. Am J Gastroenterol. 1994. 89:S116–S128.
2. Park SM, Park J, Kim JG, Yoo BC. Relevance of vacA genotypes of Helicobacter pylori to cagA status and its clinical outcome. Korean J Intern Med. 2001. 16:8–13.
3. Kim SY, Woo CW, Lee YM, Son BR, Kim JW, Chae HB, Youn SJ, Park SM. Genotyping cagA, vacA subtype, iceA1, and babA of Helicobacter pylori isolates from Korean patients, and their association with gastroduodenal diseases. J Korean Med Sci. 2001. 16:579–584.
4. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995. 55:2111–2115.
5. Atherton JC. The clinical relevance of strain types of Helicobacter pylori. Gut. 1997. 40:701–703.
6. Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995. 270:17771–17777.
7. Ji X, Fernandez T, Burroni D, Pagliaccia C, Atherton JC, Reyrat JM, Rappuoli R, Telford JL. Cell specificity of Helicobacter pylori cytotoxin is determined by a short region in the polymorphic midregion. Infect Immun. 2000. 68:3754–3757.
8. Wen S, Moss SF. Helicobacter pylori virulence factors in gastric carcinogenesis. Cancer Lett. 2009. 282:1–8.
9. Figura N, Guglielmetti P, Rossolini A, Barberi A, Cusi G, Musmanno RA, Russi M, Quaranta S. Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol. 1989. 27:225–226.
10. Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA, Berg DE. Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol. 1998. 28:37–53.
11. Rudi J, Rudy A, Maiwald M, Kuck D, Sieg A, Stremmel W. Direct determination of Helicobacter pylori vacA genotypes and cagA gene in gastric biopsies and relation to gastrointestinal disease. Am J Gastroenterol. 1999. 94:1525–1531.
12. Martínez A, González C, Kawaguchi F, Montoya R, Corvalán A, Madariaga J, Roa J, García A, Salgado F, Solar H, Palma M. Helicobacter pylori: cagA analysis and vacA genotyping in Chile. Detection of a s2/m1 strain. Rev Med Chil. 2001. 129:1147–1153.
13. Gatti LL, Fagundes e Souza EK, Leite KR, Bastos EL, Vicentini LR, Silva LC, Smith Mde A, Payão SL. cagA, vacA alleles and babA2 genotypes of Helicobacter pylori associated with gastric disease in Brazilian adult patients. Diagn Microbiol Infect Dis. 2005. 51:231–235.
14. Wu CC, Chou PY, Hu CT, Liu ZC, Lin CY, Tseng YH, Lin NT. Clinical relevance of the vacA, iceA, cagA, and flaA genes of Helicobacter pylori strains isolated in Eastern Taiwan. J Clin Microbiol. 2005. 43:2913–2915.
15. Yamazaki S, Yamakawa A, Okuda T, Ohtani M, Suto H, Ito Y, Yamazaki Y, Keida Y, Higashi H, Hatakeyama M, Azuma T. Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan. J Clin Microbiol. 2005. 43:3906–3916.
16. Nagiyev T, Yula E, Abayli B, Koksal F. Prevalence and genotypes of Helicobacter pylori in gastric biopsy specimens from patients with gastroduodenal pathologies in the Cukurova Region of Turkey. J Clin Microbiol. 2009. 47:4150–4153.
17. Yakoob J, Abid S, Abbas Z, Jafri W, Ahmad Z, Ahmed R, Islam M. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in Pakistan. BMC Gastroenterol. 2009. 9:87.
18. Jang S, Jones KR, Olsen CH, Joo YM, Yoo YJ, Chung IS, Cha JH, Merrell DS. Epidemiological link between gastric disease and polymorphisms in vacA and cagA. J Clin Microbiol. 2010. 48:559–567.
19. Ben Mansour K, Fendri C, Zribi M, Masmoudi A, Labbene M, Fillali A, Ben Mami N, Najjar T, Meherzi A, Sfar T, Burucoa C. Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients. Ann Clin Microbiol Antimicrob. 2010. 9:10.
20. Van Doorn LJ, Figueiredo C, Mégraud F, Pena S, Midolo P, Queiroz DM, Carneiro F, Vanderborght B, Pegado MD, Sanna R, De Boer W, Schneeberger PM, Correa P, Ng EK, Atherton J, Blaser MJ, Quint WG. Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology. 1999. 116:823–830.
21. Al Qabandi A, Mustafa AS, Siddique I, Khajah AK, Madda JP, Junaid TA. Distribution of vacA and cagA genotypes of Helicobacter pylori in Kuwait. Acta Trop. 2005. 93:283–288.
22. Blaser MJ, Berg DE. Helicobacter pylori genetic diversity and risk of human disease. J Clin Investig. 2001. 107:767–773.
23. Stephens JC, Stewart JA, Folwell AM, Rathbone BJ. Helicobacter pylori cagA status, vacA genotypes and ulcer disease. Eur J Gastroenterol Hepatol. 1998. 10:381–384.
24. Tiwari SK, Manoj G, Kumar GV, Sivaram G, Hassan SI, Prabhakar B, Devi U, Jalaluddin S, Kumar K, Ahmed S, Abid Z, Habeeb MA, Khan AA, Habibullah CM. Prognostic significance of genotyping Helicobacter pylori infection in patients in younger age groups with gastric cancer. Postgrad Med J. 2008. 84:193–197.
25. Letley DP, Lastovica A, Louw JA, Hawkey CJ, Atherton JC. Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: rarity of the vacA s1a genotype and natural occurrence of an s2/m1 allele. J Clin Microbiol. 1999. 37:1203–1205.
26. Aydin F, Kaklikkaya N, Ozgur O, Cubukcu K, Kilic AO, Tosun I, Erturk M. Distribution of vacA alleles and cagA status of Helicobacter pylori in peptic ulcer disease and non-ulcer dyspepsia. Clin Microbiol Infect. 2004. 10:1102–1104.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr