Combination of Helicobacter pylori Strain and Tumor Necrosis Factor‐α Polymorphism of the Host Increases the Risk of Peptic Ulcer Disease in Children

Background: Helicobacter pylori infection is probably acquired in childhood and causes a vigorous immune response. It is unclear why only a subgroup of infected children develops peptic ulcer disease. We have previously reported that iceA1 strains tend to be associated with duodenal disease in children. However, the pathogenesis probably does not depend solely on the H pylori strain but also on the variability of the host response. Objectives: The aim of this study was to assess the significance of tumor necrosis factor‐α (TNF‐α) promoter polymorphism in relation to infection with H pylori strains in children. Methods: A total of 113 antral biopsies of H pylori –positive children (ages 2–18 years) were analyzed. Of these, 23 had duodenal disease, including erosive duodenitis and/or duodenal ulceration, and 90 had gastritis only. H pylori infection was diagnosed by bacterial culture and histology. Patient genomic DNA extracted from the antral biopsy was used to characterize the genetic polymorphism of TNF‐α promoter at nucleotide positions −308 and −238 by polymerase chain reaction–based restriction fragment‐length polymorphism. All H pylori strains were examined for cytotoxin‐associated gene A and induced‐by‐contact‐with‐epithelium gene ( iceA1 ). Results: A total of 31% of children with duodenal disease were infected with iceA1 positive strains and had the −238 G to A polymorphism in the TNF‐α gene vs only 1.6% of children with gastritis alone ( P < 0.0005). Conclusions: The combination of bacterial iceA1 and TNF‐α 238 G to A polymorphism may be a risk factor for peptic ulcer disease in children infected with H pylori . Larger studies are needed to confirm this association.