HELICOBACTER PYLORI VACA, CAGA, ICEA1, AND ICEA2 GENOTYPES IN GASTROINTESTINAL DISEASES PATIENTS FROM MOSUL/IRAQ
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Objective: Helicobacter pylori is a key cause of gastroduodenal disorders, with cagA-positive strains linked to gastric cancer primarily in Western populations. Other virulent genes may enhance the effects of cagA in disease development. This study sought to identify common H. pylori virulence genes in patients with gastrointestinal disorders. Methods: Biopsy specimens were collected from 100 patients. All DNA samples underwent PCR to confirm H. pylori infection, with positive samples further genotyped. Each PCR reaction used specific primers. Results: EGD findings indicated abnormalities in 89% of patients and normal results in 11%. The gene detection rate was 77%. Analysis of 77 samples showed virulence gene prevalence as 40.3% for cagA, 46.8% for iceA1, and 31.2% for iceA2, with 76.6% containing vacA. The vacA gene was the most common, except in normal findings, where iceA1 was second, followed by cagA and iceA2. High vacA positivity was noted across various conditions, while cagA and iceA2 were absent in some patient groups. A 100% positivity rate for iceA1 was observed in patients with combined gastritis and gastric ulcers. The combination of cagA, iceA1, and vacA was observed in 20.8% of cases, while vacA and iceA1 appeared in 18.2% and vacA and iceA2 in 14.3%. Furthermore, the combination of cagA, iceA2, and vacA was found in 9.1% of cases. Conversely, the combined genotypes of cagA with iceA1, iceA2, and vacA were present at lower frequencies of 2.6%, 3.9%, and 3.9%, respectively. The individual occurrence of virulence factors varied, with vacA present in 10.4% of cases, iceA1 in 5.2%, and iceA2 in 3.9%. Additionally, cagA, iceA1, iceA2, and vacA genes were absent in 7.8% of cases. Novelty: This study reveals unique H. pylori virulence gene combinations and prevalence in Mosul, Iraq, offering regional-specific insights.
IARC Helicobacter pylori Working Group, "Helicobacter pylori eradication as a strategy for preventing gastric cancer," IARC Working Group Reports, vol. 8, 2014.
Y. Yamaoka, T. Kodama, O. Gutierrez, J. G. Kim, K. Kashima, and D. Y. Graham, "Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: Studies in four different countries," J. Clin. Microbiol., vol. 37, no. 7, pp. 2274–2279, 1999.
I. Imoto et al., "Helicobacter pylori infection: Is there circulating vacuolating cytotoxin A or cytotoxin-associated gene A protein?," Gut Pathog., vol. 14, no. 1, p. 43, 2022.
K. R. Jones, J. M. Whitmire, and D. S. Merrell, "A tale of two toxins: Helicobacter pylori CagA and VacA modulate host pathways that impact disease," Front. Microbiol., vol. 1, p. 115, 2010.
M. Hatakeyama, "Helicobacter pylori CagA and gastric cancer: A paradigm for hit-and-run carcinogenesis," Cell Host Microbe, vol. 15, no. 3, pp. 306–316, 2014.
M. Hatakeyama, "Helicobacter pylori CagA—a bacterial intruder conspiring gastric carcinogenesis," Int. J. Cancer, vol. 119, no. 6, pp. 1217–1223, 2006.
Y. Yamaoka, "Mechanisms of disease: Helicobacter pylori virulence factors," Nat. Rev. Gastroenterol. Hepatol., vol. 7, no. 11, pp. 629–641, 2010.
X. Zhu et al., "Rapid detection of cagA-positive Helicobacter pylori based on duplex recombinase aided amplification combined with lateral flow dipstick assay," Diagn. Microbiol. Infect. Dis., vol. 103, no. 1, p. 115661, 2022.
S. Maeda et al., "Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan," Gut, vol. 42, no. 3, pp. 338–343, 1998.
J. C. Atherton et al., "Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori: Association of specific vacA types with cytotoxin production and peptic ulceration," J. Biol. Chem., vol. 270, no. 30, pp. 17771–17777, 1995.
Z. Xue et al., "Geographic distribution of the cagA, vacA, iceA, oipA, and dupA genes of Helicobacter pylori strains isolated in China," Gut Pathog., vol. 13, no. 1, p. 39, 2021.
J. L. Rhead et al., "A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer," Gastroenterology, vol. 133, no. 3, pp. 926–936, 2007.
R. M. Ferreira et al., "A novel method for genotyping the Helicobacter pylori vacA intermediate region directly in gastric biopsy specimens," J. Clin. Microbiol., vol. 50, no. 12, pp. 3983–3989, 2012.
R. M. Peek Jr et al., "Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome," Proc. Assoc. Am. Physicians, vol. 110, no. 6, pp. 531–544, 1998.
P. Malfertheiner et al., "Helicobacter pylori infection," Nat. Rev. Dis. Primers, vol. 9, p. 19, 2023.
L. J. van Doorn et al., "Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori," Gastroenterology, vol. 115, no. 1, pp. 58–66, 1998.
M. T. Al-Ouqaili et al., "Study of vacuolating cytotoxin A (vacA) genotypes of ulcerogenic and non-ulcerogenic strains of Helicobacter pylori and its association with gastric disease," Saudi J. Biol. Sci., vol. 30, no. 12, p. 103867, 2023.
J. J. Lu et al., "Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastric tissues," J. Clin. Microbiol., vol. 37, no. 3, pp. 772–774, 1999.
A. A. Almehmadi and F. Alsulaimany, "A DNA sequence analysis of Helicobacter pylori in Jeddah City, Western Saudi Arabia," Int. J. Res. Pharm. Sci., vol. 11, no. 2, pp. 2758–2764, 2020.
K. D. Salman, A. N. Al-Thwaini, and B. A. Askar, "Evaluation of glmM gene in diagnosis of Helicobacter pylori with another invasive methods," Iraqi J. Biotechnol., vol. 18, no. 3, pp. 16–25, 2019.
T. R. Compaore et al., "Helicobacter pylori virulence genes cagA, babA2, and vacA detection in dyspeptic patients from Burkina Faso," Am. J. Mol. Biol., vol. 13, no. 3, pp. 141–155, 2023.
I. Brasil-Costa et al., "H. pylori infection and virulence factors cagA and vacA (s and m regions) in gastric adenocarcinoma from Pará State, Brazil," Pathogens, vol. 11, no. 4, p. 414, 2022.
N. N. T. Mai and T. H. T. Minh, "Prevalence of cagA gene and vacA genotypes of Helicobacter pylori among patients with gastroduodenal diseases," J. Med. Pharm., vol. 12, no. 1, pp. 75–81.
E. Gholamhosseinzadeh et al., "Frequency of significant virulence genes in gastric biopsies of Helicobacter pylori-positive patients with gastritis," AMB Express, vol. 13, no. 1, p. 67, 2023.
E. A. Kalaf et al., "Multiplex PCR assay for detection of Helicobacter pylori isolated from Iraqi dyspeptic patients," Iraqi J. Cancer Med. Genet., vol. 6, no. 1, pp. 49–54, 2013.
M. M. Alkherkhisy et al., "Detection of cytotoxin-associated and vacuolating cytotoxin genotypes of Helicobacter pylori in patients with peptic inflammatory/ulcerative disorders," Egyptian J. Hosp. Med., vol. 71, no. 6, pp. 3332–3342, 2018.
W. Fischer, "Assembly and molecular mode of action of the Helicobacter pylori Cag type IV secretion apparatus," FEBS J., vol. 278, no. 8, pp. 1203–1212, 2011.
F. Kamarehei et al., "Prevalence of Helicobacter pylori virulence genes among Iranian infected patients: A systematic review and meta-analysis," Rev. Res. Med. Microbiol., vol. 31, no. 4, pp. 191–200, 2020.
M. Akar et al., "Clinical relevance of virulence genes in Helicobacter pylori isolates recovered from adult dyspeptic patients in Turkey," Indian J. Med. Microbiol., vol. 40, no. 2, pp. 258–262, 2022.
S. A. Al-Jumaili et al., "Prevalence of some Helicobacter pylori virulence genes such vacA, oipA, and dupA in Iraqi patients," Res. J. Pharm. Technol., vol. 15, no. 10, pp. 4515–4518, 2022.
A. Idowu et al., "Detection of Helicobacter pylori and its virulence genes (cagA, dupA, and vacA) among patients with gastroduodenal diseases in Chris Hani Baragwanath Academic Hospital, South Africa," BMC Gastroenterol., vol. 19, no. 73, pp. 1–10, 2019.
D. M. da Costa, E. dos Santos Pereira, and S. H. B. Rabenhorst, "What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases," World J. Gastroenterol., vol. 21, no. 37, pp. 10563–10572, 2015.
L. M. Nikulina, G. A. Solovyova, and K. L. Kvacheniuk, "Clinical manifestations and comorbid conditions in patients with chronic gastritis according to Helicobacter pylori CagA and VacA status," Mod. Gastroenterol., vol. 5, no. 2, pp. 10–15, 2023.
Z. H. Alsaadi et al., "The association of cagA, vacA, babA2, babB, and oipA of Helicobacter pylori with risk of gastric carcinoma development," J. Adv. Biomed. Sci., vol. 12, no. 4, pp. 406–411, 2022.
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