H.Pylori Infection in Hispanic Children: Immune response pathway SNP pattterns

西班牙裔儿童的幽门螺杆菌感染：免疫反应途径 SNP 模式

• 批准号: 7459079
• 负责人: ERIC L BROWN
• 金额: $ 18.82万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459079
• 关键词: Abbreviations; Admixture; Adult; Affect; Age; Antibiotics; Antibodies; Bacterial Infections; Birth; Blood specimen; Body Surface Area; Body Weight; Breath Tests; Burn injury; Candidate Disease Gene; Child; Chronic; Cohort Studies; Complex; Confidence Intervals; Development; Diabetes Mellitus; Disease; Dose; Endotoxins; Environmental Risk Factor; Exposure to; Flagella; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome; Gram-Negative Bacteria; Health; Helicobacter Infections; Helicobacter pylori; Hispanics; Household; Immune response; Immunoglobulin G; Incidence; Individual; Infection; Inflammatory; Institutes; Integration Host Factors; Intervention; Invasive; Investigation; Japanese Population; Kidney Diseases; Laboratories; Life; Link; Linkage Disequilibrium; Lipopolysaccharides; Logistic Regressions; Low income; Measurement; Measures; Methods; Mexico; Molecular Target; NIH Program Announcements; Natural History; Not Hispanic or Latino; Nuclear; Odds Ratio; Organ failure; Outcome; Pathway interactions; Peptic Ulcer; Play; Population; Predisposition; Public Health; Rate; Receptor Signaling; Relative (related person); Research; Research Design; Risk; Risk Factors; Role; SEER Program; Sampling; Sepsis; Sepsis Syndrome; Seroprevalences; Serum; Siblings; Signal Transduction Pathway; Single Nucleotide Polymorphism; Stomach Carcinoma; Stomach Diseases; Subgroup; TLR4 gene; Testing; Toll-Like Receptor Pathway; Toll-like receptor 6; Toll-like receptors; Urea; cohort; cytokine; design; genetic association; genetic risk factor; health disparity; malignant stomach neoplasm; member; prevent; research study; response; transcription factor; transmission process

DESCRIPTION (provided by applicant): In Program Announcement PA-06-183: "HEALTH DISPARITIES IN NIDDK DISEASES," The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) seeks research to understand and mitigate issues of health disparities in high priority diseases within its scope, including Helicobacter pylori infection, which infects 62% of Hispanics compared to 26% in non-Hispanic whites. Persistent H. pylori infection is associated with more than 50% of peptic ulcers and is a strong risk factor for stomach cancer. Our objective is to identify genetic and environmental factors that influence acquisition and persistence of H. pylori infection in Hispanic children. We will use PASITOS (NIDDK R01-DK53664), a birth cohort of low income Hispanic children on the US-Mexico border which was established to investigate the natural history of H. pylori infection. PASITOS demonstrated that most H. pylori infections acquired early in life do not persist: so, genetic risk factors may determine infection persistence, possibly in combination with environmental factors. Recent studies have shown that the immune response plays a role in susceptibility to H. pylori infection. The toll-like receptor (TLR) signal transduction pathway regulates immune response to gram negative bacteria with flagella, including H. pylori. We hypothesize that H. pylori colonization and persistence are influenced by genetic variation in the TLR pathway as measured by single nucleotide polymorphisms (SNPs). Secondarily, we hypothesize that these same SNPs modify the effects of measures for bacterial load: that is, infection in the household. Understanding the role of genetic and environmental factors in the acquisition and persistence of H. pylori infection could help to identify subgroups that are highly susceptible to chronic H. pylori infection and determine potential molecular targets for intervention to prevent subsequent gastric disease. Specific Aims are: 1) To determine if SNPs in the TLR signal transduction pathway influence the incidence and persistence of H. pylori infection. We will take collected samples and evaluate SNPs in the TLR signal transduction pathway. A Bayesian approach will be used to estimate SNP and epistatic effects on colonization and persistence. 2) To determine if SNPs that are associated with incidence and persistence of H. pylori infection modify the effects of environmental factors associated with infection risk: in particular, bacterial load as measured by household infection levels. RELEVANCE TO PUBLIC HEALTH: While H. pylori infection rates are high in low income Hispanic children, antibiotics might not be necessary to prevent stomach diseases linked to constant infection for some children. We need to find out who will develop constant infection and treat them. Since immune response and bacterial exposure influence infection, we propose to look at related genes and household infection and how they interact to predict H. pylori infection in the PASITOS study.

描述（由申请人提供）：在计划公告PA-06-183：“NIDDK疾病的健康差异”中，美国国家糖尿病、消化和肾脏疾病研究所（NIDDK）寻求研究以了解和减轻其范围内高优先级疾病的健康差异问题，包括幽门螺杆菌感染，该感染率为62%，而非西班牙裔白人为26%。持久H.幽门螺杆菌感染与超过50%的消化性溃疡有关，并且是胃癌的一个强有力的危险因素。我们的目标是确定遗传和环境因素，影响收购和持久的H。西班牙裔儿童的幽门螺杆菌感染。我们将使用PASITOS（NIDDK R 01-DK 53664），这是一个在美墨边境低收入西班牙裔儿童的出生队列，旨在调查H.幽门感染PASITOS证明，大多数H.在生命早期获得的幽门螺杆菌感染不会持续存在：因此，遗传风险因素可能决定感染的持续性，可能与环境因素相结合。最近的研究表明，免疫应答在H.幽门感染Toll样受体（TLR）信号转导通路调节对具有鞭毛的革兰氏阴性菌（包括H。幽门。我们假设H.幽门螺杆菌的定植和持久性受到TLR途径中的遗传变异的影响，如通过单核苷酸多态性（SNP）所测量的。其次，我们假设这些相同的SNPs改变了细菌负荷测量的效果：即家庭中的感染。了解遗传和环境因素在H. pylori感染可以帮助识别对慢性H.幽门螺杆菌感染，并确定潜在的分子靶点干预，以防止随后的胃病。具体目的是：1）确定TLR信号转导通路中的SNPs是否影响H。幽门感染我们将采集样本并评估TLR信号转导通路中的SNP。贝叶斯方法将用于估计SNP和上位性对定殖和持久性的影响。2)确定与H.幽门螺杆菌感染改变了与感染风险相关的环境因素的影响：特别是通过家庭感染水平测量的细菌负荷。与公共卫生的相关性：虽然H.幽门螺杆菌感染率在低收入的西班牙裔儿童中很高，对于一些儿童来说，预防与持续感染有关的胃病可能不需要抗生素。我们需要找出谁会持续感染并治疗他们。由于免疫反应和细菌暴露影响感染，我们建议研究相关基因和家庭感染以及它们如何相互作用来预测H。pylori感染的研究。