Avaliação do padrão e número de sítos de fosforilação (EPIYA) da proteína CagA de H. pylori e risco de carcinoma gástrico e úlcera duodenal

• Ano de defesa: 2010
• Autor(a) principal: Sergio de Assis Batista
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: CagA de Hpylori; Microbiologia; Fosforilação; Helicobacter pylori; Estomago Cancer
• Link de acesso: http://hdl.handle.net/1843/ICBD-8F3MG7

Helicobacter pylori infection is considered to play an important role in the pathogenesis of gastric carcinoma and duodenal ulcer. Among the virulence factors, CagA protein has been associated with both diseases. Recently, it was described that phosphorylation of CagA occurs within tyrosine phosphorylation motifs containing EPIYA sequence. H. pylori CagA protein with higher number of EPIYA C segments has been associated with precancerous lesions and gastric carcinoma. Therefore, in this study we evaluated the number of CagA-EPIYA C segments in H.pylori strains isolated from patients with gastric carcinoma, duodenal ulcer and gastritis. We included 436 H. pylori cagA-positive patients: 188 with gastric carcinoma, 112 with duodenal ulcer and 136 with gastritis. cagA 3 variable region was PCR amplified and the results were confirmed by sequencing. Differences in the number of CagA EPIYA C segments and associations with clinical outcomes were analyzed by logistic models adjusting for age and gender. The analysis was performed by stratifying the patients into two groups: one consisted of patients colonized by cagA-positive strains with at least one EPIYA C segment and the second one included patients colonized by strains with two or more segments. Patients with gastric carcinoma were more often infected with H. pylori strains possessing more than one EPIYA C segments (41.5%) than those with gastritis (18.4%) or duodenal ulcer (13.4%). In the logistic analyses the number of EPIYA C segments remained independently associated with gastric carcinoma when patients with gastric carcinoma were compared with those with gastritis (OR = 2.81; CI 95% = 1.64 4.82; p < 10-3) or duodenal ulcer (OR = 1.79; CI 95% = 1.27 2.52; p = 0.001). However, no significant difference was observed in the number of EPIYA C segments between strains isolated from patients with duodenal ulcer and gastritis (p = 0.29). In conclusion, the results of this study showed that CagA H. pylori strains possessing higher number of EPIYA C segments were associated with increased risk of gastric carcinoma, but not of duodenal ulcer