Influence Of The IL-1B And IL-1RN Genes Polymorphisms On The Peptic Ulcer Disease

Background and ObjectiveHelicobacter pylori(H.pylori)is a major environmental fators involved in the pathogenesis of peptic ulcer,but only a small proportion of infected individuals develop the disease.the underlying pathogenic mechanisms have not been fully understood,Generally considered that the interactions between environmenta,bacterial and multiple genetic components are likely to be involved.IL-1B and IL-1RN encode IL-1βand IL-1ra,respectively. IL-1βis a pro-inflammatory cytokine,and is the powerful inhibitor of gastric acid, IL-1ra is its natural antagonist. Our aim was to investigate whether genetic polymorphisms of IL-1B-511,-31,+3954 and IL-1RN are involved in the susceptibility to peptic ulcer.MethodsThe subjects in the study involved 153 peptic ulcer patients(75 duodenal ulcer and 78 gastric ulcer) and 73 healthy volunteers. were included in peptic ulcer patients.Diagnosis of H.pylori infection was determined by both rapid urease test and histological examination(Warthin-Starry silver staining) in peptic ulcer patients,the serum H.pylori IgG was determined by ELISA in healthy volunteers. H.pylori-positive peptic ulcer patients were treated with esomeprazole 20 mg bid, amoxicillin 1.0 bid, clarithromycin 0.5 bid for 7 days,1 weeks later, treated with esomeprazole 20mg bid for 3 weeks. H.pylori-negative peptic ulcer patients were treated with esomeprazole 20 mg bid for 4 weeks. we observed the healing by gastroscopy in all of the peptic ulcer patients at 2 weeks posttreatment.IL-1B-511,-31,+3954 and IL-1RN polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) .Results1)The positive rate of H.pylori infection in duodenal ulcer patients was 96.0%,significantly higher than the healthy controls(65.8%),the odds ratio(OR)was 12.50(95%CI为3.57~43.72), H.pylori positive of gastric ulcer was 79.5%,there was no significant differences in H.pylori infection between gastric ulcer and healthy controls(P>0.05).2)The genotype frequencies of IL-1B-511,IL-1B-31,IL-1B+3954 and IL-1RN were conformed to Hardy-weinberg Equilibrium both in the control population and patient group.3)There were no significant differences in the gene polymorphism of IL-1B-511,-31,+3954 between duodenal ulcer or gastric ulcer patients and healthy controls(P>0.05).In addition, no significant differences with the simultaneous carriage of IL-1B-511* C,IL-1B-31*T and IL-1B+3954*C alleles between duodenal ulcer or gastric ulcer patients and healthy controls(P>0.05).4)The gene frequency of allele 2 of IL-1RN in duodenal ulcer patients was significantly higher than that in healthy controls(19.3% vs 9.8%,P=0.046) , the OR of the IL-1RN L/2 and IL-1RN2/2 genotypes was 2.31(95%CI=1.07~4.98).With H. pylori positive, the gene frequency of allele 2 of IL-1RN in duodenal ulcer patients was significantly higher than that in healthy controls (P=0.024) , the OR of the IL-1RN L/2 and IL-1RN2/2 genotype was 3.29(95%CI=1.22~8.83). There were no significant differences in the IL-1RN*2 gene frequencies between gastric ulcer and healthy controls ( P > 0.05).5)After adjusted for age,sex and smoking by logistic regression,the OR of H.pylori and allele 2 of IL-1RN in the development of duodenal ulcer was 3.97(95%CI=1.53~10.34) and 18.01(95%CI =4.70~69.67), respectively.6)At 2 weeks posttreatment, there were no significant differences in the gene polymorphism of IL-1B-511,-31,+3954 and IL-1RN between healing patients and nonhealing patient with duodenal ulcer or gastric ulcer(P>0.05).In addition,no significant differences with the simultaneous carriage of IL-1B-511* C,IL-1B-31* T and IL-1B+3954*C alleles between healing patients and nonhealing patient with duodenal ulcer or gastric ulcer(P>0.05).Conclusion1)Our date verified IL-1RN*2 as an independent factor that govern the development of duodenal ulcer.2)H.pylori infection and IL-1RN*2 synergistic determined susceptibility to duodenal ulcer.3)No association was observed between the polymorphisms of IL-1B or IL-1RN and gastric ulcer.4)The polymorphisms of IL-1B and IL-1RN didn't affect the ulcer healing on the early phase of esomeprazole administration.