M Wilschanski1, J Faber1, B Rudensky2, S Freier1, E Feigin3, D Halle2
1Pediatric Gastroenterology Unit, 2Microbiology Laboratory, 3Surgery A, Shaare Zedek Medical Center , Jerusalem, Israel.
Helicobacter pylori (H.pylori) infection is probably acquired in childhood and it causes a vigorous immune response. It is unclear as to why some infected people eventually develop clinical pathology like peptic ulcer disease and gastric cancer and others do not. The solution does not depend solely on pathogenic strains of H.pylori but also on the variability of the host response. Tumor necrosis factor alpha (TNF-alpha) is a potent pro-inflammatory cytokine which has been implicated in chronicity of inflammation and gastritis. Several SNP (single nucleotide polymorphisms) in the promoter region of the TNF-alpha gene have been implicated in TNF production.
Aim: The aim of this study was to assess the significance of TNF-alpha promoter polymorphism in relation to infection with H.pylori in children.
Methods: 134 children (aged 2-18 years) underwent upper endoscopy, 102 were H.pylori positive of which 12 had duodenitis/ulcer; 32 uninfected children were controls. H.pylori infection was diagnosed by bacterial culture, histology and rapid urease test. Antral biopsy DNA was used to characterize the genetic polymorphism of TNF-alpha promoter at nucleotide positions 308 and 238 by PCR- based restriction fragment length polymorphism.
Results: G to A transition at position 238 or 308 of the TNF-alpha promoter gene was not associated with H.pylori infection or cagA subtype status in contrast to a previous publication (J Clin Pathol 2001 54:703-6). However, in H.pylori infected children carrying the G to A transition at position 238 there was a trend towards an association with duodenal disease, 25% of children with duodenal disease had this polymorphism, vs. only 11% carriage in children with gastritis ( Fishers exact test ).
Conclusion: TNF-alpha-238A polymorphism may be a risk factor for peptic ulcer disease in children infected with H.pylori . Further studies are needed to confirm this association.
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