Association of nonsynonymous substitutions in the intermediate region of the vacA gene of Helicobacter pylori with gastric diseases in Taiwan.
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ABSTRACT:
SUBMITTER: Sheu SM
PROVIDER: S-EPMC2620866 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
Publications
Association of nonsynonymous substitutions in the intermediate region of the vacA gene of Helicobacter pylori with gastric diseases in Taiwan.
Sheu Shew-Meei SM Hung Kuei-Hsiang KH Sheu Bor-Shyang BS Yang Hsiao-Bai HB Wu Jiunn-Jong JJ
Journal of clinical microbiology 20081119 1
The amino acid sequences corresponding to the vacA intermediate region from 39 isolates of Helicobacter pylori were investigated. The substitution of a G for the third S in the i1-type cluster B sequence (QASEGITSSK) conferred a greater risk of gastric diseases (P < 0.03; Fisher's exact test). The conserved substitutions of an F for the Y in the cluster A sequence and of an M for the second N in the i1-type cluster C sequence could be a marker of VacA in the Taiwanese strains. ...[more]
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Project description:BackgroundPathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein.ResultsWe identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis.ConclusionsPrediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.
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Project description:Objective:The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods:Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of. Results:H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of vacA, babA2, and oipA genes and their association with clinical outcomes. vacA, babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82. Conclusion:In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes.
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Project description:The diversity of the gene encoding the vacuolating cytotoxin (vacA) of Helicobacter pylori was analyzed in 98 isolates obtained from different geographic locations. The studies focused on variation in the previously defined s and m regions of vacA, as determined by PCR and direct sequencing. Phylogenetic analysis revealed the existence of four distinct types of s-region alleles: aside from the previously described s1a, s1b, and s2 allelic types, a novel subtype, designated s1c, was found. Subtype s1c was observed exclusively in isolates from East Asia and appears to be the major s1 allele in that part of the world. Three different allelic forms (m1, m2a, and m2b) were detected in the m region. On the basis of sequence alignments, universal PCR primers that allow effective amplification of the s and m regions from H. pylori isolates from all over the world were defined. Amplimers were subsequently analyzed by reverse hybridization onto a line probe assay (LiPA) that allows the simultaneous and highly specific hybridization of the different vacA s- and m-region alleles and tests for the presence of the cytotoxin-associated gene (cagA). This PCR-LiPA method permits rapid analysis of the vacA and cagA status of H. pylori strains for clinical and epidemiological studies and will facilitate identification of any further variations.
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