Inverse association between a pro-inflammatory genetic profile and Helicobacter pylori seropositivity among patients with chronic atrophic gastritis: Enhanced elimination of the infection during disease progression?

Abstract

Helicobacter pylori infection is a key risk factor for chronic atrophic gastritis (CAG), an established precursor of gastric cancer. There is increasing evidence of frequent clearance of the infection during progression of CAG. We aimed to assess the association between host inflammatory polymorphisms and H. pylori seropositivity among CAG patients from Germany. In the baseline examination of ESTHER, a population-based study conducted in Saarland, serum pepsinogens I and II and H. pylori serostatus were measured by ELISA, and selected genetic polymorphisms (IL1A C-889T, IL1B C-511T, IL1RN A9589T, IL8 T-251A, IL10 T-819C, IL10 A-1082G, LTA C+80A and TNFA G-308A) were assessed by Pyrosequencing for 534 serologically defined CAG cases. H. pylori seropositivity strongly decreased with disease severity, which is defined by quintiles of serum pepsinogen I, from higher than 90% in the least severe cases to hardly over 50% in the most severe cases. The pro-inflammatory genotypes IL10 -819CC and IL1RN 9589TT were significantly associated with decreased H. pylori seroprevalences with odds ratios of 0.45 (95% confidence interval (CI): 0.23-0.88) and 0.41 (95% CI: 0.18-0.92), respectively, after controlling for age, sex and disease severity. H. pylori seropositivity decreased with the number of pro-inflammatory genotypes (p<0.01). Our results disclose a clear inverse association between a pro-inflammatory genetic profile and H. pylori seropositivity among cases with CAG, supporting suggestions of enhanced elimination of H. pylori during the development of the disease.