Cytokine gene polymorphisms and the pathology of chronic gastritis

Abstract

Introduction: Helicobacter pylori (H. pylori) infection is associated with divergent clinical outcomes and these outcomes are largely influenced by the levels of cytokines in the gastric mucosa. The levels of these cytokines are dependant on cytokine gene polymorphisms. Pro-inflammatory cytokine polymorphisms are strongly associated with severe histological changes in the gastric mucosa in Caucasian populations.

Methods: In this study, we evaluated the role of cytokine gene polymorphisms in influencing the pathological severity of gastritis. 120 patients were evaluated. Cytokine gene polymorphisms of interleukin-1 (IL-1) beta, tumour necrosis factor alpha and the IL-1 receptor antagonist genes were done using polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR variable number of tandem repeats markers typed on the deoxyribonucleic acid obtained from the peripheral blood. Histological analysis was done by using the revised Sydney system.

Results: There was no association between pro-inflammatory cytokine gene polymorphisms and severity of gastritis.

Conclusion: This data suggests that high cytokine levels are not seen in the gastric mucosa in Indians in spite of H. pylori colonisation. IL-1 beta is a potent proinflammatory cytokine which causes a partial clearance of the organism as well as hypochlorhydria. Corporal hypochlorhydria causes a persistent colonisation by H. pylori followed by the development of gastric atrophy and later carcinoma. This lack of association with a pro-inflammatory polymorphism suggests that only low levels of IL-1 beta are present in the gastric mucosa. This causes a low clearance of the organism and a high incidence of duodenal ulceration because of hyperchlorhydria. However, it is protective against the development of gastric carcinoma. This would explain the "Indian Paradox" of the apparent discrepancy of a high degree of colonisation by H. pylori and a low incidence of gastric carcinoma in the Indian population.