The EPIYA-ABCC motif pattern in CagA of Helicobacter pyloriis associated with peptic ulcer and gastric cancer in Mexican population

Abstract

BackgroundHelicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer.MethodsA total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3′ variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer.ResultsH. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3–15.1; p < 0.001) and gastric cancer (OR = 5.9, 95% CI = 1.5–22.1) were significantly increased in individuals who harbored the EPIYA-ABCC cagA gene pattern.ConclusionscagA-positive H. pylori is highly prevalent in southern Mexico, and all CagA variants were of the western type. The cagA alleles that code for EPIYA-ABCC motif patterns are associated with peptic ulcers and gastric cancer.

Detection of Helicobacter pylori CagA EPIYA in gastric biopsy specimens and its relation to gastric diseases

“…A significant association similar between peptic ulcer (54.5%) and CagA variants carrying 2 or more EPIYA C also was detected in Mexico, recently (Beltrán-Anaya et al, 2014). These data are consistent with other studies, and the presence of a larger number of CagA EPIYA-C segments is considered a risk factor for gastroduodenal ulceration (Panayotopoulou et al, 2010;Salih et al, 2010).…”

“…Thus, determining the CagA type found in each H. pylori infection may confer additional benefit to previously identify populations that have a higher risk of developing peptic ulcer and gastric cancer (Beltrán-Anaya et al, 2014;Huang et al, 2003). Therefore, the aim of Diagnostic Microbiology and Infectious Disease xxx (2015) xxx-xxx this study is to investigate whether the presence of CagA EPIYA variations in H. pylori is related to differing degrees of gastric mucosal disease in patients from south Brazil.…”

Pathobiology of Helicobacter pylori–Induced Gastric Cancer

“…These tyrosine phosphorylation domains are classified as EPIYA- A, B, C, or D, and differ between Western strains (containing A, B, and C domains) and East Asian strains (containing A, B, and D domains) 31 . The number and types of repeats have been associated with differing risks of carcinogenesis 58 . Recently, it was reported that the EPIYA-B motif binds and activates PI3-kinase and AKT, but many Western strains of H pylori carry a single nucleotide polymorphism in this domain that reduces its association with PI3 kinase and also reduces the risk of gastric cancer 59 .…”

Helicobacter pylori, úlcera péptica y cáncer gástrico

“…Las diferencias en las manifestaciones clínicas y la gravedad de las enfermedades gástricas dependen de la virulencia de H. pylori, conferida especialmente por los genes cag A, vac A, dup A, ice A, oip A y bab A, los cuales se consideran predictores de resultados clínicos graves (39,40). El gen Vac A está asociado a la expresión de citotoxinas y su análisis estructural muestra dos regiones: la región señal (s) y la región media (m); a su vez, la primera está dividida en los subtipos s1a, s1b y s2, algunos de los cuales han sido asociados a enfermedades como úlcera péptica y cáncer gástrico.…”

“…Los genes cag A, vac A, dup A, ice A, oip A y bab A han mostrado ser predictores de resultados clínicos graves (1,39,(42)(43)(44). La presencia del genotipo vac A-s1 se asocia con una mayor frecuencia de úlcera péptica, mientras que el genotipo cag A se asocia en su mayoría con gastritis crónica atrófica y adenocarcinoma gástrico (1,40,44,45). La relación de cag A con úlcera péptica puede ser manifestación de su expresión conjunta con el genotipo vacA-s1 (1,46).…”