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Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients.

ABSTRACT: BACKGROUND AND AIMS: The Helicobacter pylori CagA gene is a major virulence factor that plays an important role in gastric pathologies. The size variation of CagA gene, which is dependent on the 3' repeat region, contains one or more Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs and CagA multimerization (CM) motifs. Four segments flanking the EPIYA motifs, EPIYA -A, -B, -C, or -D, were reported to play a crucial role in the pathogenesis of H. pylori infection. The aim was to determine the roles of EPIYA segments and CM motifs in gastroduodenal pathogenesis in an Iraqi population. PATIENTS AND METHODS: Gastric biopsies were collected from 210 patients with gastritis, duodenal ulcer (DU), gastric ulcer (GU), and gastric cancer (GC). The EPIYA motif genotyping was determined by polymerase chain reaction and sequencing. The differences in age, gender, and CagA EPIYA motifs of H. pylori between GC, DU, GU and gastritis patients were analyzed using a ?(2) -test. RESULTS: A total of 22 (45.8%) strains had three copies of EPIYA (ABC type), 2 (4.16%) had four copies (ABCC type), 6 (12.7%) had five copies (ABCCC type), 13 (27.08%) had two copies (AB type), 3 (6.25%) had the BC, and 2 (4.17%) had AC motif. The alignment of the deduced protein sequences confirmed that there were no East Asian type EPIYA-D sequences in Iraqi strains. A significant association was found between increase in number of EPIYA-C motifs and GU (P ? 0.01) compared with gastritis. CONCLUSIONS: The structure of the 3' region of the CagA gene in Iraqi strains was Western type with a variable number of EPIYA-C and CM motifs. A significant association was found between increase in number of EPIYA-C motifs and GU compared with gastritis indicating predictive association with the severity of the disease. The GenBank accession numbers for the partial CagA nucleotide sequences determined in this study are JX164093-JX164112.

SUBMITTER: Kalaf EA

PROVIDER: S-EPMC3632013 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature

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Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients.

Kalaf Elham A EA Al-Khafaji Zahra M ZM Yassen Nahi Y NY Al-Abbudi Fadel A FA Sadwen Saad N SN

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20130301 2

<h4>Background and aims</h4>The Helicobacter pylori CagA gene is a major virulence factor that plays an important role in gastric pathologies. The size variation of CagA gene, which is dependent on the 3' repeat region, contains one or more Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs and CagA multimerization (CM) motifs. Four segments flanking the EPIYA motifs, EPIYA -A, -B, -C, or -D, were reported to play a crucial role in the pathogenesis of H. pylori infection. The aim was to determine the roles of E ...[more]

PMID: 23481132

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Project description:BackgroundAs a marker of Helicobacter pylori, Cytotoxin-associated gene A (cagA) has been revealed to be the major virulence factor causing gastroduodenal diseases. However, the molecular mechanisms that underlie the development of different gastroduodenal diseases caused by cagA-positive H. pylori infection remain unknown. Current studies are limited to the evaluation of the correlation between diseases and the number of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in the CagA strain. To further understand the relationship between CagA sequence and its virulence to gastric cancer, we proposed a systematic entropy-based approach to identify the cancer-related residues in the intervening regions of CagA and employed a supervised machine learning method for cancer and non-cancer cases classification.MethodologyAn entropy-based calculation was used to detect key residues of CagA intervening sequences as the gastric cancer biomarker. For each residue, both combinatorial entropy and background entropy were calculated, and the entropy difference was used as the criterion for feature residue selection. The feature values were then fed into Support Vector Machines (SVM) with the Radial Basis Function (RBF) kernel, and two parameters were tuned to obtain the optimal F value by using grid search. Two other popular sequence classification methods, the BLAST and HMMER, were also applied to the same data for comparison.ConclusionOur method achieved 76% and 71% classification accuracy for Western and East Asian subtypes, respectively, which performed significantly better than BLAST and HMMER. This research indicates that small variations of amino acids in those important residues might lead to the virulence variance of CagA strains resulting in different gastroduodenal diseases. This study provides not only a useful tool to predict the correlation between the novel CagA strain and diseases, but also a general new framework for detecting biological sequence biomarkers in population studies.

Dataset Information

Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients.

Publications

Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients.

Similar Datasets

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