title: Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa.
abstract: Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1β and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.
authors.affiliation: Facultad de Ciencias Químicas, Universidad La Salle A.C., Mexico City, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Trejo-de la O
authors.affiliation: Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.affiliation: Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, SS, Mexico City, Mexico Laboratorio de Bacteriología Médica, Escuela Nacional de Ciencias Biológicas-IPN, Mexico City, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Sánchez-Zauco
authors.affiliation: Unidad de Investigación en Inmunología, CMN SXXI, IMSS, Mexico City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Pérez-Rodríguez
authors.affiliation: Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Camorlinga-Ponce
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Mor., México.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Flores-Luna
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Mor., México.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lazcano-Ponce
authors.affiliation: Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, SS, Mexico City, Mexico cmaldobe@yahoo.com.
authors.forename: Carmen
authors.initials: C
authors.lastname: Maldonado-Bernal
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D004381:Duodenal Ulcer / Q000235:genetics / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051198:Toll-Like Receptor 5 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: D016207:Cytokines; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9
keywords: Duodenal ulcer; Helicobacter pylori; Toll-like receptor 9; gastric cancer; single-nucleotide polymorphisms