Helicobacter Pylori Infection And Host IL-1 Genetic Polymorphisms Interaction In Development Of Duodenal Ulcer

Helicobacter pylori has been researched deep since World Health Organization's International Agency for Research on Cancer concluded that it is one of the grade I carcinogen in humans. But the epidemiological studies shows that not all persons who infected H. pylori will develop gastric adenocarcinomas or ulcer. Genomic organization and sequence of H.pylori is genetically diverse as well as the distribution of genotype is diverse in different region and race, which cause variable clinical outcome. In addition, human genetic polymorphisms is in association with H. pylori-associated diseases.Based on the Mathematical Model of Blaser that the ultima pathological consequences depended on the interplay of host and bacterial genetic polymorphism. IL-1β is an important inflammatory factor and a potent inhibitor of gastric acid secretion in stomach. Specific genetic polymorphisms in the IL-1B and IL-1RN genes will affect IL-1β level, lead to different host response and clinical disease.In this study, we observed distribution character of IL-1B and IL-1RN gene polymorphisms in Henan Province and studied the gene polymorphisms difference between DUs and controls to identify the relationship of DU and HP infection, Du and host gene polymorphisms of IL-1B or IL-1RN, interaction of HP infection and gene polymorphisms of IL-1.Materials and Methods1 Study objectsA total number of 243 unrelated Han patients attending hospital and spouses of some patients (153 males, 90 females; age range from 15 to 87 years) were studied. All persons knew and consented to join in the investigation. A number of 148 persons (54 DUs, 94 controls) were analyzed in case-control study. All study objects written a questionnaire which including basic information, disease history, lifestyle, family history, psychology, et al.2 ELISASerum samples were analyzed by ELISA and were performed according to the manufacturer's instructions. Immunoglobulin G antibody were determined by enzyme marking instrument in 450 nm, if P/N ^2.1 then result was positive, if P/N< 2.1 then result was negative.3 PCR-RFLPThe IL-1B-31 and IL-1B-511 gene was amplified by PCR. PCR products were determined by RFLP using Alul (AG I CT) and AvaI(C I CCGAG) respectively. IL-1B-31 PCR product was 239 bp, the restriction fragments (234 bp for allele C, 137 bp and 97 bp for allele T). IL-1B-511 PCR product was 517 bp, the restriction fragments (517 bp for allele T, 331 bp and 186 bp for allele C). The PCR products and the restriction fragments were separated by electrophoresis on agarose gel and stained with ethidium bromide.4 The VNTR polymorphism of the IL-1RNIntron 2 of IL-1RN gene was PCR amplified using the new primers pair. PCR products were separated by electrophoresis on 2% agarose gel and stained with ethidium bromide. The different IL-1RN alleles were named following the nomenclature proposed by El-Omar. In particular: if the longth of PCR product was 633 bp (four repeats) was named allele I ; allele II was 461 bp (two repeats); allele III was 719 bp (five repeats); allele IV was 547 bp (three repeats); allele V was805 bp (six repeats). 5 Statistical analysisQuestionnaire and lab results were input using Foxpro. The statistical analysis was made using /-test, Fisher's exact test, chi-square test, nonparametric test ( Wilcoxon ), Unconditional logistic regression analysis.Results1 Distributions of interleukin-1 beta and interleukin-1 receptor antagonistgene polymorphisms in Henan Han populationGenotype frequencies of these two polymorphisms did not deviate significantly from Hardy-Weinberg expectation in the group.In Hennan Han people, the gene frequence of IL-lB-31 C allele was 59% and the T allele was 41%, C/T genotype frequence was the highest one(42%). The gene frequence of IL-1B-511 T allele was 56% and the C allele was 44%. C/T genotype frequence was the highest one(43%). The gene frequency of IL-1RN I allele was higher (0.899), While IL-1RN II allele was lower(0.078), III allele(0.002) and IV allele(0.02) were infrequent. Compared with other regions, the gene frequency of IL-lB-31, IL-1B-511, IL-1RN in Henan Han population was similar with east-Asia. and different with the west.2 case-control studyCharacteristics of DU cases and controls were matched except sex. Males were at more risk than females. Smoking and drinking were risk factor of DU. HP infection was associated with DU cases (P=0.0001 and OR=8.26). significant association was found between DU and the IL- 1B-511C/C (P=0.02, OR=3.05).The results showed that there were interaction between IL-1B-31T/T and HP infection,OR=16.75,P=0.0003, EREI=6.42, AP=0.38, y =1.22.IL-1B-31T/T could stimulate dangerous effect of HP infection when person infected with HP and exposed to IL-1B-31T/T simultaneously. IL-1B-511C/C had similar effect with IL-1B-31T/T,OR=41.42,/><0.0001. But IL-1RN could reduce the risk effect ofHP,OR=4.93, y=0. 84. Conclusion1 The gene frequency of IL-1B-31, IL-1B-511, IL-1RN in Henan Han population issimilar with east-Asia, and different with the west.2 Smoking and drinking are risk factor of DU. Males are at more risk than females. HP infection is an risk factor of DU.3 In this study, gene polymorphisms of IL-1B-511C/C is associated with DU, the result is due to the interaction between IL-1B-511C/C and HP infection possibly.4 Interaction is statistical significance between IL-1B-31T/T and HP, IL-1B-511C/C and HP infection, IL-1RN and HP. IL-1B-31T/T, IL-1B-511C/C could stimulate risk effect of HP, But IL-1RN could reduce the risk effect of HP.