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Risk Factors Analysis and Polymorphisms of Correlated Genes of H.pylori Infection Population

Author: GuoXin
Tutor: ZhaoBaoHua
School: Hebei Normal
Course: Biochemistry and Molecular Biology
Keywords: Helicobacter pylori gene polymorphism T-lymphocyte subset CD27 CD70
CLC: R378
Type: PhD thesis
Year: 2010
Downloads: 55
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Abstract

Helicobacter pylori(H.pylori)is the only bacteria that parasites in human gastric tissue. The populations are generally susceptible to it.After Marshall and Warren reported their success in culturing the H. pylor from gastric mucosa in patients in 1984, soon H. pylor was proved to be an important cause of gastrointestinal disease and was highly carcinogenic. World Health Organization Cancer Center announces that H. pylori infection can increase morbidity and mortality of gastric cancer and classify it as carcinogen in 1994. H. pylori is the first prokaryotic carcinogenic proved. In the same year the U.S.National Institutes of Health propose that antibiotics for H. pylori should be included in the course of curing common stomach disease.H. pylori infection is the major causes of gastritis, gastric ulcer, gastric cancer and other gastrointestinal diseases. However, only a small fraction of colonized individuals, representing at least half of the world’s population, develop gastric cancer. The interplay between bacterial and host gene polymorphisms may explain why gastric cancer only occurs in a small fraction of H. pylori-infected individuals.Here we analyse host immune respone and genetic factors in the H. pylori infection,comparise those profiles with clinical and pathological data,we think those data may contribute to a better understanding of the pathophysiological mechanisns of the H. pylori infection and the identification of gene associated with the infection.Objective To invest the prevalence and the main subtypes of H. pylori in Hebei and explore the effects that the H. pylori infection contributing to the host immune system,then analyse the host immune respone and gene polymorphism in the H.pylori infection. Establish association between gene allele and the risk for H.pylori infection. Single-nucleotide polymorphism analysis may identify those individuals who would suffer gastric cancer after H. pylori infection and find new genes may associate with the infection.Methods 1.Cllecting the pathological data by a unified questionnaire in the Second Hospital of Hebei Medical University between 2007～2009, H. pylori IgG antibody is examinated by enzyme linked immunosorbent assay (ELISA), gastric biopsy are used for the H. pylori culture and H. pylori gene subtype determination. PCR is used to determine the popular subtype of H. pylori in Hebei by 9 pairs of primers. Serum specimens were used for anti-H. pylori IgG test and other serum tests.2.Using immunohistochemistry and flow cytometry to measure H. pylori antibody, IL-2,IL-10 and the number of CD3+,CD4+,CD8+ T cells of gastritis, gastric ulcer and gastric cancer patinets.Immune responses are assessed by T cell counts and the cytokines.3.According to the DNA sequence of CD27 and CD70 and SNP informations published from NCBI, Searches restriction enzyme with DNASIS v2.5 Demo, use online tools TFSEARCH to define the transcription factor binding sites,at last, We select six SNPs of CD27 and CD70,such as:rs3087273,rs3136550, rs2532507, rs60982224, rs7253697, rs1808398, measure those SNPs in patients with or without H. pylori infection,analyse these genes polymorphism in both groups.Results 1.Epidemiological investigation and clinical characteristics of the sample results show that H. pylori infection rate was 54.5% in Hebei adult population and the infection rate is various, it infects more man than woman, older than the young.H.pylori infection is associated with atherosclerosis, hyperlipidemia and hyperglycemia.H. pylori VacA-positive strains is the main genetype in Hebei, VacA-positive strain is 80.00% in gastritis people and 100% in ulcers.CagA strain is 66.67% in gastritis people.The most common strain of H. pylori is VacA-s1a-m2, then VacA-s1b-m2.2. Immunohistochemistry and flow cytometry results show that Comparing with control people,IL-2 is lower in serum specimens and gastric biopsy of gastritis, ulcers and gastric people, the gastric people which H. pylori is positive express lower IL-2 than gastritis,and the expression of CD3+,CD4+, CD4+/CD8+ also significantly lower than the control group in gastric people.3.Polymerase chain reaction-restriction fragment length polymorphism results show that the rs3087273 AG genotype, rs3136550 CC genotypes, rs 2532570 GG genotype, rs 11808398 CC genotype are lower in the H. pylori infection patients than control group. The carriage of that allele may be associated with a decreased risk for H.pylori-related gastric cancer development in Hebei.Conclusion In this study we find that H. pylori infection rate was 54.5% and VacA-positive strains is the main genetype in Hebei,and the most common strain of H. pylori is VacA-sla-m2 subtype. H. pylori infection affects the patients immune respone and breaks the balance between Thl and Th2 cells, which may contribute to persistence of the bacteria and increase the risk of gastric in H. pylori infection people.Host gene polymorphisms are also associated with H. pylori infection.Our results suggest the polymorphism of rs3087273, rs3136550, rs 2532570 and rs 11808398 may be involved in the H. pylori infection diease. In addition, our results shed light on the interplay between H. pylori and host susceptibility factors in the induction of gastric cancer.More studies are needed to invest the inflammatory mechanisms involved in the H. pylori-host interaction.

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