Characterization of virulence factor dupA, of Helicobacter pylori, genotyping and analysis of the expression of genes of tumor necrosis factor and E-cadherin in samples of children and adults with symptoms peptides

• Grant number: 12/18333-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2012
• End date: October 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Lucas Trevizani Rasmussen
• Grantee: Lucas Trevizani Rasmussen
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Sagrado Coração (USC). Bauru , SP, Brazil
• Associated researchers: João Paulo Bianchi Ximenez ; Juliana Garcia de Oliveira Cucolo ; Marilanda Ferreira Bellini ; Marilia de Arruda Cardoso Smith ; Roger William de Labio ; Spencer Luiz Marques Payão

Abstract

Helicobacter pylori (H. pylori) is a Gram-negative bacterium, which persistently colonizes gastric mucosa of humans and plays an important role in the initiation of gastrointestinal diseases, particularly peptic and duodenal ulcers, as well as gastric cancer and lymphoid tissue (MALT) lymphoma. Host-pathogen interactions involving environmental, host, and bacterial factors seem to contribute to the onset and progression of gastric disease. Extensive search for H. pylori virulence factors leads to the characterization of an associated cytotoxin A (cagA) that has been shown to be involved in induction of proinflammatory chemokine released by the host cell; a vacuolating cytotoxin A (vacA) that induces the formation of vacuole in mammalian cells in vitro; and duodenal ulcer promoting gene A (dupA) that has been associated with duodenal ulceration and increased gastric inflammation. The host genetic factors include cytokines, and some studies demonstrate that TNF acts as a potent inhibitor of gastric secretion after Helicobacter pylori infection contributing to the development of gastric diseases, and acting as the most powerful mediator of acute inflammatory response against Gram-negative bacterium. Studies have also associated E-cadherin with the infiltrative and metastatic capacity of tumors in which the loss of cell - cell interaction mediated by E-cadherin is a prerequisite for tumor invasion. Infection with H. pylori appears to induce gene inactivation of E-cadherin, being associated with the pathogenesis of gastric tumors. Therefore, the aims of this study are: To characterize the promoter region polymorphism -308 (rs1800629) of TNF by PCR-RFLP; to detect the presence of genes dupA by PCR and analysis the gene expression of TNF and E-cadherin genes in 620 samples from gastric biopsies of adults and pediatric patients with peptic symptoms and / or gastric cancer, in order to correlate genotypes involved in the expression of genes involved and dupA virulence factor in the development and in the progression of gastric changes. The development of this approach may open new perspectives for the characterization of factors involved in peptic diseases, gene regulation, as well as to elucidate the interaction among genes involved in gastric diseases, improving the understanding of the pathophysiological mechanisms of these diseases. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZABAGLIA, LUANNA MUNHOZ; FERRAZ, MARIANE AVANTE; PEREIRA, WEENDELLY NAYARA; ORCINI, WILSON APARECIDO; DE LABIO, ROGER WILLIAN; NETO, AGOSTINHO CALEMAN; WISNIESKI, FERNANDA; DE OLIVEIRA, JULIANA GARCIA; CARDOSO SMITH, MARILIA DE ARRUDA; MARQUES PAYAO, SPENCER LUIZ; et al. Lack of association among TNF-alpha gene expression,-308 polymorphism (G > A) and virulence markers of Helicobacter pylori. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 21, DEC 30 2015. (12/18333-3, 13/21224-4, 13/21285-3)

LUANNA MUNHOZ ZABAGLIA; MARIANE AVANTE FERRAZ; WEENDELLY NAYARA PEREIRA; WILSON APARECIDO ORCINI; ROGER WILLIAN DE LABIO; AGOSTINHO CALEMAN NETO; FERNANDA WISNIESKI; JULIANA GARCIA DE OLIVEIRA; MARILIA DE ARRUDA CARDOSO SMITH; SPENCER LUIZ MARQUES PAYÃO; et al. Lack of association among TNF-α gene expression, -308 polymorphism (G > A) and virulence markers of Helicobacter pylori. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 21, 2015-12-31. (12/18333-3, 13/21224-4, 13/21285-3)

PEREIRA, WEENDELLY NAYARA; FERRAZ, MARIANE AVANTE; ZABAGLIA, LUANNA MUNHOZ; DE LABIO, ROGER WILLIAM; ORCINI, WILSON APARECIDO; BIANCHI XIMENEZ, JOAO PAULO; NETO, AGOSTINHO CALEMAN; MARQUES PAYAO, SPENCER LUIZ; RASMUSSEN, LUCAS TREVIZANI. Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 20, JAN 23 2014. (12/18333-3)

PEREIRA, WEENDELLY NAYARA; FERRAZ, MARIANE AVANTE; ZABAGLIA, LUANNA MUNHOZ; DE LABIO, ROGER WILLIAM; ORCINI, WILSON APARECIDO; BIANCHI XIMENEZ, JOAO PAULO; NETO, AGOSTINHO CALEMAN; MARQUES PAYAO, SPENCER LUIZ; RASMUSSEN, LUCAS TREVIZANI. Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 20, p. 5-pg., 2014-01-23. (12/18333-3)