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Introduction
Helicobacter pylori (H. pylori) colonizes the gastric mucosa of the human stomach and establishes long-term infection. Dyspepsia is the most common gastrointestinal disorder, and is the most common indication for gastric endoscopy [1]. Infection with H. pylori have been proven to be highly associated with gastritis, peptic ulcer disease (PUD) and adenocarcinoma [2,3]. Since 1994, The World Health Organization (WHO) classified H. pylori as Class I carcinogen because of its causal relationship to gastric carcinoma [4-6]. The extent and the severity of these associations depend on several elements, such as bacterial virulence factors, age of the host, genetic susceptibility, immune response and environmental factors [7].
H. pylori has a number of virulence factors that play a role in its pathogenicity and influence its colonization and disease severity. CagA, encoded by cagA gene is a part and a marker of cagA Pathogenicity Island (PAI). CagA-positiveH. pyloristrains are associated with severe inflammation and increased risk of ulcers and cancer in humans. The presence of cagA usually coincide with the presence of other virulence factors, including vacA[8,9]. VacA is an H. pylori toxin with multiple cellular effects in different host cell types. Virtually all H. pylori strains produce VacA. However, there is significant variation among strains in their capacity to induce cell vacuolization. This variation is attributed to the genetic structural diversity of the vacA gene that can assume different polymorphic rearrangements [10]. The initial studies on vacA detected two main polymorphic regions; the signal (s)- and the middle (m)- regions. The s- region assumes two forms s1 or s2 allele and the m-region encoded the vacA m1 or m2 allele. The vacA type s1 strains appear to be more active than s2 strains and are found more frequently in ulcer disease. The vacA m1 type strains are associated with greater gastric epithelial damage than m2 strains. The combination of s- and m-region allelic types determines the production of the cytotoxin and is associated with pathogenicity of H. pylori strains. vacA s1/m1 strains produce a large amount of toxin, s1/m2 strains produce moderate amounts and s2/m2 strains produce very little or no toxin [11-13].
The iceA gene has two main allelic variants; iceA1 and iceA2. The expression of iceA1...