Synergistic effect of IL-1β and TNF-α polymorphisms on the H. pylori-related gastric pre-malignant condition.

Abstract

We investigated the effect of IL-1β and TNF-α polymorphisms, and its synergistic effect with age, gender and H. pylori status on the gastric pre-malignant condition. IL-1β-31(T>C) and -511(C>T) and TNF-α-857 (C>T) polymorphisms were genotyped in 123 cancer free subjects. Degree of histological gastritis in both antrum and corpus, and extension of endoscopic gastric atrophy were also evaluated. Significant associations were found between degrees of mononuclear cell infiltration (p=0.007) and atrophy (p=0.01) in the antrum with IL-1β-31(T>C) polymorphism, and degree of endoscopic gastric atrophy with both IL-1β-31(T>C), -511(C>T) polymorphisms (p=0.03, 0.04, respectively). When subjects were divided into the 3 groups according to the histological severity of gastric mucosal atrophy: the non-atrophic gastritis (NA) group (atrophy score=0 and metaplasia score=0), the severe atrophic gastritis (SA) group (atrophy score>=2 or metaplasia score>=2), and the mild atrophic gastritis (MA) group (all others), synergistic effect was found between numbers of IL-1β-31C, IL-1β-511T variant alleles with co-factors on the development of gastric atrophy in the antrum (gender + H. pylori + number of IL-1β-31C allele: p=0.001, age + gender + H. pylori + number of IL-1β-31C allele: p=0.0008, gender + H. pylori + number of IL-1β-511T allele: p=0.016, age + gender + H. pylori + number of IL-1β-511T allele: p=0.013), while such association was found for TNF-α-857 T allele in the antrum and all genotypes in the corpus. IL-1β-31C, IL-1β-511T variant alleles may accelerate gastric mucosal inflammation and atrophy, not only by themselves, but also through the interaction with co-factors.