covid
Buscar en
Revista Colombiana de Cancerología
Toda la web
Inicio Revista Colombiana de Cancerología Relación entre la integridad del CagPAI y los polimorfismos en el gen CagA con ...
Información de la revista
Vol. 16. Núm. 2.
Páginas 110-118 (enero 2011)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 16. Núm. 2.
Páginas 110-118 (enero 2011)
Acceso a texto completo
Relación entre la integridad del CagPAI y los polimorfismos en el gen CagA con la severidad de la gastritis en pacientes infectados con H. pylori CagA positivo
The Relation between CagPAI Integrity and the Polymorphisms in the CagA Gene with the Severity of Gastritis in Patients Infected With CagA-Positive H. pylori
Visitas
3159
María M. Bravo1,
Autor para correspondencia
mbravo@cancer.gov.co

Correspondencia María Mercedes Bravo, Instituto Nacional de Cancerología, Avenida 1a No. 9-85, Bogotá, D. C., Colombia. Teléfono (571) 334 1111 Ext. 4220.
, Teresa Martínez2, Juan C. Bravo3
1 Grupo de Investigación en Cáncer y Agentes Infecciosos, Instituto Nacional de Cancerología, Bogotá, D. C., Colombia
2 Grupo Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá, D. C., Colombia
3 Departamento de Patología, Fundación Valle del Lili, Santiago de Cali, Valle, Colombia
Este artículo ha recibido
Información del artículo
Resumen
Objetivos

Evaluar la histopatología gástrica en pacientes colombianos con gastritis infectados con Helicobacter pylori CagA-positivo y su asociación a la integridad del islote de patogenicidad Cag (CagPAI) y el número de motivos EPIYA-C presentes en la proteína CagA.

Métodos

Se incluyó a 31 individuos con diagnóstico de gastritis. A partir de biopsias gástricas se aisló H. pylori CagA-positivo y se caracterizó, mediante secuencia, la composición de motivos EPIYA. La histopatología fue evaluada según el sistema Sidney actualizado. Los genes CagA, CagT, CagE y Cag10 fueron genotipificados mediante PCR y electroforesis en agarosa.

Resultados

En total, 24 aislamientos (el 77% de los casos) portaban CagPAI íntegro. De los aislamientos negativos para uno o más genes del CagPAI, 7 de ellos (22%) fueron considerados como portadores de un CagPAI defectuoso. No se observaron diferencias significativas en los promedios de densidad de H. pylori, el grado de inflamación crónica ni la presencia de atrofia glandular o de metaplasia intestinal entre aislamientos con el CagPAI íntegro, en comparación con aislamientos con el CagPAI defectuoso. Tampoco se observaron diferencias significativas en los parámetros histopatológicos entre los aislamientos con un motivo EPIYA-C o más de un motivo EPIYA-C, ni en antro ni en cuerpo, excepto para la infiltración por neutrófilos, que fue significativamente mayor en cuerpo en aislamientos con más de un motivo EPIYA-C (p=0,018).

Conclusiones

No se halló asociación entre la diversidad en los factores de virulencia CagPAI y CagA de aislamientos colombianos, y los hallazgos histopatológicos en la gastritis, otros factores del hospedero o ambientales podrían afectar las características histopatológicas de la gastritis.

Palabras clave:
Helicobacter pylori
gastritis
factores de virulencia
polimorfismo genético
Abstract
Objectives

To evaluate gastric histopathology in Colombian patients infected with CagA-positive Helicobacter pylori and its association with the integrity of Cag (CagPAI) pathogenicity island and the number of EPIYA-C motifs present in the CagA protein.

Methods

Thirty-one (31) individuals diagnosed with gastritis were included in the study. Using gastric biopsies, CagA-positive H.pylori was isolated and EPIYA motif makeup was characterized by sequencing. Histopathology was evaluated with updated Sydney system. The CagA, CagT, CagE and Cag10 genes were genotyped using PCR and agarose electrophoresis.

Results

A total of 24 isolates (77% of cases) carried a complete CagPAI. Among the negative isolates for one or more genes with CagPAI, 7 (22%) were considered to be carriers of a defective CagPAI. No significant differences were observed in H. pylori density averages, degree of chronic inflammation, presence of glandular atrophy or intestinal metaplasia between isolates with complete CagPAI and isolates with defective CagPAI. No significant differences were observed in the histopathological parameters between isolates with one EPIYAC motif and those with more than one EPIYA-C motif, neither in antrum nor in body, except for infiltration by neutrophils which was significantly greater in bodies with isolates with more than one EPIYA-C motif (p=0.018).

Conclusions

No association was found between the diversity of virulence CagPAI and CagA factors in Colombian isolates and the histopathological findings in gastritis, or in other host or environmental factors that could affect the histopathological characteristics of gastritis.

Key words:
Helicobacter Pylori
gastritis
virulence factors
polymorphism
genetic
El Texto completo está disponible en PDF
Referencias
[1.]
M.J. Blaser.
Ecology of Helicobacter pylori in the human stomach.
J Clin Invest, 100 (1997), pp. 759-762
[2.]
IARC working Group on the evaluation of Carcinogenic Risks to Humans.
Schistosomes liver flukes and Helicobacter pylori.
International Agency for Research on Cancer, (1994),
[3.]
D.J. McGee, H.L. Mobley.
Pathogenesis of Hel icobacter pylori infection.
Curr Opin Gastroenterol, 16 (2000), pp. 24-31
[4.]
M.J. Blaser, G.I. Perez-Perez, H. Kleanthous, et al.
Infection with Helicobacter pylori strains possessing CagA is associated with an increased risk of developing adenocarcinoma of the stomach.
Cancer Res, 55 (1995), pp. 2111-2115
[5.]
A.J. Quiroga, D.M. Cittelly, M.M. Bravo.
BabA2, oipA and CagE Helicobacter pylori genotypes in Colombian patients with gastroduodenal diseases.
Biomédica, 25 (2005), pp. 325-334
[6.]
S. Censini, C. Lange, Z. Xiang, J.E. Crabtree, P. Ghiara, M. Borodovsky, et al.
Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and diseaseassociated virulence factors.
Proc Natl Acad Sci USA, 93 (1996), pp. 14648-14653
[7.]
N.S. Akopyants, S.W. Clifton, D. Kersulyte, et al.
Analyses of the Cag pathogenicity island of Helicobacter pylori.
Mol Microbiol, 28 (1998), pp. 37-53
[8.]
M.K. Tummuru, T.L. Cover, M.J. Blaser.
Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production.
Infect Immun, 61 (1993), pp. 1799-1809
[9.]
M. Stein, R. Rappuoli, A. Covacci.
Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after Cagdriven host cell translocation.
Proc Natl Acad Sci USA, 97 (2000), pp. 1263-1268
[10.]
H. Higashi, R. Tsutsumi, S. Muto, et al.
SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.
Science, 295 (2002), pp. 683-686
[11.]
M. Hatakeyama.
Oncogenic mechanisms of the Helicobacter pylori CagA protein.
Nat Rev Cancer, 4 (2004), pp. 688-694
[12.]
H. Higashi, R. Tsutsumi, A. Fujita, et al.
Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites.
Proc Natl Acad Sci U S A, 99 (2002), pp. 14428-14433
[13.]
R.H. Argent, M. Kidd, R.J. Owen, et al.
Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori.
Gastroenterology, 127 (2004), pp. 514-523
[14.]
R.H. Argent, J.L. Hale, E.M. El-Omar, et al.
Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion.
J Med Microbiol, 57 (2008), pp. 1062-1067
[15.]
N. Acosta, A. Quiroga, P. Delgado, et al.
Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis.
World J Gastroenterol, 16 (2010), pp. 3936-3943
[16.]
M.F. Dixon, R.M. Genta, J.H. Yardley, et al.
Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994.
Am J Surg Pathol, 20 (1996), pp. 1161-1181
[17.]
M.K. Tummuru, S.A. Sharma, M.J. Blaser.
Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells.
Mol Microbiol, 18 (1995), pp. 867-876
[18.]
S. Maeda, H. Yoshida, T. Ikenoue, et al.
Structure of Cag pathogenicity island in Japanese Helicobacter pylori isolates.
Gut, 44 (1999), pp. 336-341
[19.]
S. Suerbaum, P. Michetti.
Helicobacter pylori infection.
N Engl J Med, 347 (2002), pp. 1175-1186
[20.]
R.M. Peek Jr., M.J. Blaser.
Helicobacter pylori and gastrointestinal tract adenocarcinomas.
Nat Rev Cancer, 2 (2002), pp. 28-37
[21.]
M.J. Blaser, D.E. Berg.
Helicobacter pylori genetic diversity and risk of human disease.
J Clin Invest, 107 (2001), pp. 767-773
[22.]
D.A. Israel, R.M. Peek.
Pathogenesis of Helicobacter pyloriinduced gastric inflammation.
Aliment Pharmacol Ther, 15 (2001), pp. 1271-1290
[23.]
Helicobacter and Cancer Collaborative Group.
Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts3.
Gut, 49 (2001), pp. 347-353
[24.]
S. Honda, T. Fujioka, M. Tokieda, et al.
Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils.
Cancer Res, 58 (1998), pp. 4255-4259
[25.]
E.J. Kuipers, G.I. Pérez-Pérez, S.G. Meuwissen, et al.
Helicobacter pylori and atrophic gastritis: importance of the CagA status.
J Natl Cancer Inst, 87 (1995), pp. 1777-1780
[26.]
J.F. Weel, R.W. van der Hulst, Y. Gerrits, et al.
The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related diseases.
J Infect Dis, 173 (1996), pp. 1171-1175
[27.]
L.E. Bravo, L.J. van Doom, J.L. Realpe, et al.
Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma?.
Am J Gastroenterol, 97 (2002), pp. 2839-2842
[28.]
A.J. Quiroga, A. Huertas, A.L. Cómbita, et al.
Variation in the number of EPIYA-C repeats in CagA protein from Colombian Helicobacter pylori strains and its ability middle to induce hummingbird phenotype in gastric epithelial cells.
Biomédica, 30 (2010), pp. 251-258
[29.]
P.I. Hsu, I.R. Hwang, D. Cittelly, et al.
Clinical presentation in relation to diversity within the Helicobacter pylori Cag pathogenicity island5.
Am J Gastroenterol, 97 (2002), pp. 2231-2238
[30.]
F. Kauser, A.A. Khan, M.A. Hussain, et al.
The Cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human populations.
J Clin Microbiol, 42 (2004), pp. 5302-5308
[31.]
L.T. Nguyen, T. Uchida, Y. Tsukamoto, et al.
Clinical relevance of CagPAI intactness in Helicobacter pylori isolates from Vietnam.
Eur J Clin Microbiol Infect Dis, 29 (2010), pp. 651-660
[32.]
T. Shimoyama, J.E. Crabtree.
Mucosal chemokines in Helicobacter pylori infection.
J Physiol Pharmacol, 48 (1997), pp. 315-323
[33.]
H. Umit, A. Tezel, S. Bukavaz, et al.
The relationship between virulence factors of Helicobacter pylori and severity of gastritis in infected patients.
Dig Dis Sci, 54 (2009), pp. 103-110
[34.]
N. Schneider, U. Krishna, J. Romero-Gallo, et al.
Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential.
J Infect Dis, 199 (2009), pp. 1218-1221
[35.]
L.A. Sicinschi, P. Correa, R.M. Peek, et al.
CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.
Clin Microbiol Infect, 16 (2010), pp. 369-378
[36.]
Y. Yamaoka, H.M. El-Zimaity, O. Gutiérrez, et al.
Relationship between the CagA 3’ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH.
Gastroenterology, 117 (1999), pp. 342-349
[37.]
C. Rizzato, J. Torres, M. Plummer, et al.
Variations in helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention.
PLoS One, 7 (2012), pp. e2960-e2965
[38.]
A. Reyes-León, J.C. Atherton, R.H. Argent, et al.
Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the CagA gene.
Infect Immun, 75 (2007), pp. 3445-3454
[39.]
D.N. Sgouras, E.G. Panayotopoulou, K. Papadakos, et al.
CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children.
J Clin Microbiol, 47 (2009), pp. 2426-2434
Copyright © 2012. Instituto Nacional de Cancerología
Descargar PDF
Opciones de artículo