CagA, and vacA alleles and sites of tyrosine phosphorylation of CagA protein of H. pylori in patients with and without family history of gastric cancer

• Main Author: Cicero Igor Simoes Moura Silva
• Other Authors: LÃcia LibanÃz Bessa Campelo Braga
• Format: Others
• Language: Portuguese
• Published: Universidade Federal do Cearà 2009
• Subjects: FARMACIA
• Online Access: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4086

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior === The H. Pylori strains demonstrate a high level of phenotypic and genotypic diversity, the expression of various genes, which confer greater pathogenicity to the bacteria. Relatives of patients with gastric cancer have a higher risk of developing gastric diseases, especially if they are infected with more virulent strains of H. pylori. The objective was to characterize the strains of H. pylori, the presence of genes vacA, cagA, and sites of tyrosine phosphorylation of CagA protein - EPIYA in patients with and without family history of gastric cancer, and correlate the presence of the cagA gene to the level of activity and inflammation chronic gastritis. The genotyping of strains of H. pylori was performed by PCR and sequencing of the phosphorylation sites EPIYA. We evaluated 94 biopsy samples of gastric mucosa from dyspeptic patients H. pylori positive, 55 with a family history of gastric cancer and 39 without family history. All genotyped strains were vacA positive, and 45.7% with the vacA allele s1m1; s1m2 vacA 26.6%, 4.3% were vacA s2m1; 10.6% vacA s2m2; 3 hybrid strains and 9 (9.6 %) showed only the allele sequence signal (s). Of the 94 strains genotyped 87.2% were cagA positive, with no statistical difference between groups of familiar and unfamiliar (92.7% vs 82.0%, p = 0.058). The cagA gene was present in most patients with gastritis, with statistical significance in the group of relatives of cancer (p = 0.004). The degree of activity and inflammation of gastritis, was more significant in the group of patients with cagA positive strains, with pangastritis Corpal and gastritis. In the antrum, there were significant only in relation to the activity of gastritis. The studed strains, 93.9% showed EPIYA phosphorylation sites, with 59.2% of these had only one site, 38.2% with two sites and 2.6% with three sites. There was no statistical difference in the number of sites EPIYA between the groups. It is important to genetically characterize the strains of H. pylori to establish clearly its role in different clinical conditions related to it. Keywords: H. pylori. === Cepas de H. pylori demonstram um alto nÃvel de diversidade fenotÃpica e genotÃpica, pela expressÃo de vÃrios genes, que conferem maior patogenicidade à bactÃria. Familiares de pacientes com cÃncer gÃstrico tÃm maior risco de desenvolver doenÃas gÃstricas, principalmente se forem infectados por cepas mais virulentas de H. pylori. O objetivo foi caracterizar as cepas de H. pylori, quanto à presenÃa dos genes vacA, cagA e dos sÃtios de fosforilaÃÃo de tirosina da proteÃna CagA â EPIYA, em pacientes com e sem histÃria familiar de cÃncer gÃstrico, e correlacionar a presenÃa do gene cagA com o grau de atividade e de inflamaÃÃo da gastrite crÃnica. A genotipagem das cepas de H. pylori foi realizada atravÃs da tÃcnica de PCR e do sequenciamento dos sÃtios de fosforilaÃÃo EPIYA. Foram avaliados 94 fragmentos de biÃpsia de mucosa gÃstrica provenientes de pacientes dispÃpticos H. pylori positivo, 55 com histÃria familiar de cÃncer gÃstrico e 39 sem historia familiar. Todas as cepas genotipadas foram vacA positivas, sendo 45,7% com o alelo vacA s1m1; 26,6% vacA s1m2; 4,3% eram vacA s2m1; 10,6% vacA s2m2; 3 cepas hÃbridas e 9 (9,6%) apresentaram somente o alelo da sequÃncia sinal(s). Das 94 cepas genotipadas 87,2% foram cagA positivas, nÃo havendo diferenÃa estatÃstica entre os grupos de familiares e nÃo familiares (92,7% vs 82,0%; p= 0.058). O gene cagA estava presente na maioria dos pacientes portadores de gastrite, havendo significÃncia estatÃstica no grupo dos familiares de cÃncer (p= 0,004). O grau de atividade e inflamaÃÃo da gastrite, foi mais significante no grupo de pacientes com cepas cagA positivo, com pangastrite e gastrite corpal. No antro, somente houve significÃncia com relaÃÃo à atividade da gastrite. Das cepas estudadas, 93,9% apresentaram sÃtios de fosforilaÃÃo EPIYA, sendo que 59,2% destas apresentaram somente um sitio, 38,2% com dois sÃtios e 2,6% com trÃs sÃtios. NÃo houve diferenÃa estatÃstica com relaÃÃo ao nÃmero de sÃtios EPIYA, entre os grupos estudados. à importante a caracterizaÃÃo genÃtica das cepas de H. pylori para se estabelecer com clareza o seu papel nos diversos quadros clÃnicos a ele relacionado