Association Between Polymorphisms Of IL-1 And TNF-α Genes And H. Pylori-Associated Gastroduodenal Diseases

Objective: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood, the host genetic factor might play an important role in the pathogenesis of gastroduodenal diseases. Interleukin-1 and tumor necrosis factor-αis a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to discuss the polymorphisms of IL-1 and TNF-αgenes and their association with H.pylori-associated gastroduodenal diseases in Han people.Methods : H.pylori-positive 142 patients with H.pylori-associated gastroduodenal diseases(38 chronic gastritis, 30 duodenal ulcer, 39 gastric ulcer, 35 gastric cancer) and 70 healthy controls with H.pylori positive were genotyped for IL-1B-511,TNF-A-308,TNF-A-857 gene polymorphisms by the PCR-RFLP method.Results:In this population, both IL-1B-511 and TNF-A-857 site existed C/T polymorphism, their genotypes were C/C,T/T,C/T. TNF-A-308 site existsed A/G polymorphism, its genotypes were A/A,G/G,G/A.The genotypes of IL-1RN were 1/1,1/2,1/4,4/4.The results indicated that the frequencies of IL-1B-511and IL-1RN genotypes in diseases group were not significantly different compared with control group(P>0.05).The frequencies of TNF-A-308 genotypes in chronic gastritis group , gastric ulcer group and gastric cancer group were significantly different compared with control group (χ2=22.614,P<0.001;χ2=19.317,P<0.001;χ2=16.062,P<0.001).TNF-A-857 genotypes in duodenal ulcer group and gastric ulcer group were significantly different too(χ2=9.444, P=0.009;χ2=11.702, P=0.003).Multivariate logistic regression analysis showed that the subjects carrying the TNF-A-308 A/A genotype were at a 22-fold elevated risk for chronic gastritis(OR=22.70, 95%CI:2.51-205.40)and at a 21-fold elevated risk for gastric ulcer (OR=21.62, 95%CI: 2.07-226.13)and at a 16-fold elevated risk for gastric cancer (OR=16.41,95%CI:1.62-116.55)compared with the subjects carrying TNF-A-308G/G. The subjects carrying the TNF-A-857 T/T genotype were at a 6-fold elevated risk for duodenal ulcer (OR=6.73, 95%CI: 1.71-26.53) and at a 5-fold elevated risk for gastric ulcer (OR=5.37, 95%CI: 1.28-22.50) compared with the subjects carrying TNF-A-857 T/T.Conclusions: The results suggest that the polymorphism of IL-1B-511and IL-1RN gene has no association with H.pylori-associated gastroduodenal diseases and with susceptibility of gastric cancer,the polymorphism of TNF-αgene has close association with H.pylori-associated gastroduodenal diseases and with susceptibility of gastric cancer.