Abstract
Duodenal ulcers in children are associated with Helicobacter pylori gastric infection with cagA-positive strains, but factors linked to the host are poorly known. The authors evaluated the role of proinflammatory interleukin-1 gene cluster polymorphisms in the pathogenesis of duodenal ulcer. They studied prospectively 437 children 1 to years old, 209 of whom were H. pylori positive and 228 of whom were H. pylori negative. IL1B-511-C/T, -31T/C, and IL1RN Variable number of tandem repeats were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism, PCR with confronting two-pair primers, and PCR, respectively. cagA status was evaluated by PCR. The role of the proinflammatory cytokine genotypes in the genesis of duodenal ulcer was evaluated before and after stratification of H. pylori status on logistic regression models. In the group of children without duodenal ulcer, no association was observed between H. pylori status and proinflammatory polymorphisms. Furthermore, no association between IL1 cluster genotypes and cagA status was seen in the H. pylori-positive children. However, increasing age, male sex, and IL1RN*2 were independently associated with duodenal ulcer. After stratification, in the H. pylori-positive children, increasing age, male sex, the presence of ILRN*2 allele, and cagA-positive status were independently associated with duodenal ulcer. The risk for the development of duodenal ulcer increased when a combined association of the presence of IL1RN*2 allele and infection by a cagA-positive H. pylori strain was the variable. This study provides evidence supporting independent roles of IL1RN*2 allele and cagA-positive status in the genesis of duodenal ulcer in children.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- cagA:
-
cytotoxin-associated gene
- CI:
-
confidence interval
- DU:
-
duodenal ulcer
- IL:
-
interleukin
- IL1RN:
-
interleukin-1 receptor antagonist gene
- OR:
-
odds ratio
- PAI:
-
pathogenicity island
- PCR:
-
polymerase chain reaction
- VacA:
-
vacuolating cytotoxin
References
Mégraud F, Lamouliatte H 1992 Helicobacter pylori and duodenal ulcer: evidence suggesting causation. Dig Dis Sci 37: 769–772
Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK 1992 Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325: 1127–1131
Wotherspoon AC, Ortiz-Hidalgo O, Falzon MR, Isaacson PG 1991 Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 338: 1175–1176
Drumm B 1993 Helicobacter pylori in the pediatric patient. Gastroenterol Clin North Am 169: 162–182
Nogueira AM, Cabral MM, Carvalho AS, Oliveira CA, Queiroz DM, Oliveira AM, Rocha GA, Mendes EN, Magalhães PP, Castro AM, Paturle P 2000 Gastrite associada ao Helicobacter pylori em adultos e crianças: estudo comparativo. J Bras Patol 36: 110–117
Queiroz DM, Mendes EM, Carvalho AS, Rocha GA, Oliveira AM, Soares TF, Santos A, Cabral MM, Nogueira AM 2000 Factors Associated with Helicobacter pylori infection by a cagA-positive strain in children. J Infect Dis 181: 626–630
De Gusmão VR, Nogueira Mendes E, De Magalhaes Queiroz DM, Aguiar Rocha G, Camargos Rocha AM, Ramadan Ashour AA, Carvalho AS 2000 vacA genotypes in Helicobacter pylori strains isolated from children with and without duodenal ulcer in Brazil. J Clin Microbiol 38: 2853–2857
Rocha GA, Rocha AM, de Magalhaes Queiroz D, Nogueira Mendes E, Nogueira AM, Teles de Carvalho AS 2001 Validation of a commercial enzyme-linked immunosorbent assay to detect anti-cagA antibodies in children with Helicobacter pylori infection. J Pediatr Gastroenterol 33: 515–518
Crabtree JE, Covacci A, Farmery SM, Xiang Z, Tompkins DS, Perry S, Lindley IJ, Rappuoli R 1995 Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype. J Clin Pathol 48: 41–45
Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A 1996 Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93: 14648–14653
Montecucco C, de Bernard M 2003 Immunosuppressive and proinflammatory activities of the VacA toxin of Helicobacter pylori.. J Exp Med 198: 1767–1771
El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS 2000 Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404: 398–402
Machado JC, Pharoah P, Sousa S, Carvalho R, Oliveira C, Figueiredo C, Amorim A, Seruca R, Caldas C, Carneiro F, Sobrinho-Simões M 2001 Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 121: 823–829
Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simões M 2002 Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94: 1680–1687
Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, Gerhard M, Prinz C 2004 Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut 53: 1082–1090
El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, Stanford JL, Mayne ST, Goedert J, Blot WJ, Fraumeni JF Jr, Chow WH 2003 Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 124: 1193–1201
Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SD 2003 Color and genomic ancestry in Brazilians. Proc Natl Acad Sci U S A 100: 177–182
Queiroz DM, Mendes EN, Rocha GA 1987 Indicator medium for isolation of Campylobacter pylori.. J Clin Microbiol 25: 2378–2379
de Carvalho Costa Cardinali L, Rocha GA, Rocha AM, de Moura SB, de Figueiredo Soares T, Esteves AM, Nogueira AM, Cabral MM, de Carvalho AS, Bittencourt P, Ferreira A, Queiroz DM 2003 Evaluation of [13C] urea breath test and Helicobacter pylori stool antigen test for diagnosis of H. pylori infection in children from a developing country. J Clin Microbiol 41: 3334–3335
Monteiro L, Gras N, Vidal R, Cabrita J, Mégraud F 2001 Detection of Helicobacter pylori DNA in human feces by PCR: DNA stability and removal of inhibitors. J Microbiol Methods 45: 89–94
Kelly SM, Pitcher MC, Farmery SM, Gibson GR 1994 Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom. Gastroenterology 107: 1671–1674
Peek RM Jr, Miller GG, Tham K, Pérez-Pérez GI, Cover TL, Atherton JC, Dunn GD, Blaser MJ 1995 Detection of Helicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol 33: 28–32
Clayton CL, Kleanthous H, Coates PJ, Morgan DD, Tabaqchali S 1992 Sensitive detection of Helicobacter pylori by using polymerase chain reaction. J Clin Microbiol 30: 192–200
Hamajima N, Matsuo K, Saito T, Tajima K, Okuma K, Yamao K, Tominaga S 2001 Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection. Jpn J Cancer Res 92: 383–389
Mansfield JC, Holden H, Tarlow JK, Di Giovine FS, McDowell TL, Wilson AG, Holdsworth CD, Duff GW 1994 Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 106: 637–642
Hosmer DW, Lemeshow S 2000 Applied Logistic Regression. JH Wiley Interscience Publication, New York, pp 143–202
Oderda G, Figura N, Bayeli PF, Bassagni C, Bugnule M, Arnellini D, Altare F, Ansaldi N 1993 Serologic IgG recognition of Helicobacter pylori cytotoxin-associated protein, peptic ulcer and gastroduodenal pathology in childhood. Eur J Gastroenterol Hepatol 5: 695–699
Blanchard SS, Bauman L, Czinn SJ 2004 Treatment of Helicobacter pylori in pediatrics. Curr Treat Options Gastroenterol 7: 407–412
Evans DG, Queiroz DM, Mendes EN, Evans DJ Jr 1998 Helicobacter pylori cagA status and s and m alleles of vacA in isolates from individuals with a variety of H. pylori-associated gastric diseases. J Clin Microbiol 36: 3435–3437
Dinarello CA 1996 Biologic basis for interleukin-1 in disease. Blood 87: 2095–2147
Hwang IR, Kodoma T, Kikuchi S, Sakai K, Peterson LE, Graham DY, Yamaoka Y 2002 Effect of Interleukin 1 polymorphisms on gastric mucosal Interleukin 1β production in Helicobacter pylori infection. Gastroenterology 123: 1793–1803
Santtila S, Savinainen K, Hurme M 1998 Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 47: 195–198
Queiroz DM, Moura SB, Mendes EN, Rocha GA, Barbosa AJ, de Carvalho AS 1994 Effect of Helicobacter pylori eradication on G-cell and D-cell density in children. Lancet 343: 1191–1194
Queiroz DM, Mendes EN, Rocha GA, Moura SB, Resende LM, Barbosa AJ, Coelho LG, Passos MC, Castro LP, Oliveira CA, Lima GF Jr 1993 Effect of Helicobacter pylori eradication on antral gastrin- and somatostatin-immunoreactive cell density and gastrin and somatostatin concentrations. Scand J Gastroenterol 28: 858–864
El-Omar EM 2001 The importance of interleukin 1[beta] in Helicobacter pylori associated disease. Gut 48: 743–747
Furuta T, El-Omar EM, Xiao F, Shirai N, Takashima M, Sugimura H, Sugimurra H 2002 Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology 123: 92–105
Garcia-Gonzales MA, Lanas A, Santolaria Crusius BA, Serrano MT, Pena AS 2001 The polymorphic IL-1B and IL-1RN gene in the aetiopathogenesis of peptic ulcer. Clin Exp Immunol 125: 368–375
Zambon CF, Basso D, Navaglia G, Germano G, Gallo N, Milazzo M, Greco E, Fogar P, Mazza S, Di Mario F, Basso G, Rugge M, Plebani M 2002 Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia. Cytokine 18: 242–251
Queiroz DM, Guerra JB, Rocha GA, Rocha AM, Santos A, De Oliveira AG, Cabral MM, Nogueira AM, De Oliveira CA 2004 IL1B and IL1RN polymorphic genes and Helicobacter pylori cag A strains decrease the risk of reflux esophagitis. Gastroenterology 127: 73–79
Queiroz DM, Rocha GA, Mendes EN, Carvalho AS, Barbosa AJ, Oliveira CA, Lima GF Jr 1991 Differences in distribution and severity of Helicobacter pylori gastritis in children and adults with duodenal ulcer disease. J Pediatr Gastroenterol Nut 12: 178–181
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by CNPq and FAPEMIG, Brazil
Rights and permissions
About this article
Cite this article
Queiroz, D., Bittencourt, P., Guerra, J. et al. IL1RN Polymorphism and cagA-Positive Helicobacter pylori Strains Increase the Risk of Duodenal Ulcer in Children. Pediatr Res 58, 892–896 (2005). https://doi.org/10.1203/01.PDR.0000181380.14230.8B
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000181380.14230.8B
