IL-1 Family Gene Polymorphisms and Susceptibility to P. aeruginosa in CF Patients

CF患者IL-1家族基因多态性与铜绿假单胞菌易感性

基本信息

批准号：
8051794
负责人：
HARA LEVY
金额：
$ 18.75万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8051794
关键词：
Accounting Affect Age Alginates Alleles Antibodies Bacterial Infections Cell physiology Chronic Clinical Collaborations Complex Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator DNA Databases Data Defect Deterioration Development Diagnostic Enrollment Ensure Failure Family Gender Gene Cluster Gene Family Gene Frequency Genes Genetic Genetic Polymorphism Genetic Variation Genotype Heterogeneity IL1B gene Immune response Immunity Immunologic Factors Infection Inflammation Inflammatory Inflammatory Response Interleukin-1 Interleukin-1 Receptors Interleukin-1 alpha Lung Lung diseases Maintenance Measures Mediating Mediator of activation protein Molecular Target Morbidity - disease rate Mucins Natural Immunity Neonatal Screening Outcome Patients Phenotype Play Predisposition Prevalence Production Pseudomonas Pseudomonas Infections Pseudomonas aeruginosa Pulmonary Cystic Fibrosis Pulmonary Function Test/Forced Expiratory Volume 1 Reporting Reproducibility Research Design Resistance Respiratory physiology Role Sampling Serum Severity of illness Single Nucleotide Polymorphism Surface Antigens Testing Transmembrane Transport Variant Wisconsin Work airway inflammation anakinra base case control cohort cystic fibrosis patients follow-up genetic association genetic risk factor genetic variant immunopathology mortality mucoid novel prognostic programs public health relevance pulmonary function response tool

项目摘要

DESCRIPTION (provided by applicant): This project will evaluate genetic variants within the interleukin 1 (IL-1) gene cluster (IL-1 alpha, beta, IL-1 receptor and IL-1 receptor antagonist) that may impact the presence of alginate-specific opsonic antibody and lack of detectable mucoid Pseudomonas colonization. One factor accounting for heterogeneity in cystic fibrosis (CF) pulmonary disease is suspected to be genetic variation in the IL-1 gene family, which plays a role in mediating innate immunity to P. aeruginosa infection and potentially influences levels of opsonic antibody. Overall, the project will test whether polymorphisms within specific genes in the IL-1 gene cluster represent potential modifying factors that account for phenotypic heterogeneity as measured by the presence or absence of both opsonic antibodies and mucoid P. aeruginosa colonization in CF patients with the ?F508 genotype. A case-control genetic association study design will be used to test for association of variation in the IL-1 gene cluster with the presence or absence of opsonic antibodies and mucoid Pseudomonas. An assessment will then be made on the reproducibility of the genetic associations in two additional family-based CF cohorts. Our unique multicenter collaboration, incorporating CF patients enrolled in the Wisconsin Newborn Screening Program, will ensure needed longitudinal follow-up of young patients necessary to confirm current findings and define complex associations. The resulting data will define the expression of opsonic antibodies in early infections of the CF lung by mucoid P. aeruginosa and the contribution of host response to clinical outcome. This project has several important implications for identification of functional genetic variation in novel molecular targets and development of novel clinical diagnostic and prognostic tools. PUBLIC HEALTH RELEVANCE: Cystic Fibrosis (CF) lung disease is characterized by chronic infection by Pseudomonas aeruginosa and is the major cause of morbidity and mortality in CF patients. The resulting data will define the expression of opsonic antibodies in early infections of the CF lung by mucoid P. aeruginosa and the contribution of host response to clinical outcome. This project has several important implications for identification of functional genetic variation in novel molecular targets and development of novel clinical diagnostic and prognostic tools.

描述（由申请人提供）：该项目将评估白细胞介素 1 (IL-1) 基因簇（IL-1 α、β、IL-1 受体和 IL-1 受体拮抗剂）内可能影响藻酸盐存在的遗传变异-特异性调理性抗体和缺乏可检测的粘液假单胞菌定植。导致囊性纤维化 (CF) 肺病异质性的一个因素被怀疑是 IL-1 基因家族的遗传变异，该基因家族在介导铜绿假单胞菌感染的先天免疫中发挥作用，并可能影响调理性抗体的水平。总体而言，该项目将测试 IL-1 基因簇中特定基因内的多态性是否代表了解释表型异质性的潜在修饰因素，表型异质性是通过 CF 患者中是否存在调理性抗体和粘液铜绿假单胞菌定植来衡量的。 F508 基因型。病例对照遗传关联研究设计将用于测试 IL-1 基因簇变异与调理性抗体和粘液假单胞菌存在或不存在的关联。然后将对另外两个基于家庭的 CF 队列中遗传关联的重现性进行评估。我们独特的多中心合作，包括参加威斯康星州新生儿筛查计划的 CF 患者，将确保对年轻患者进行必要的纵向随访，以确认当前的发现并确定复杂的关联。由此产生的数据将定义调理性抗体在粘液铜绿假单胞菌肺部早期感染中的调理抗体的表达以及宿主反应对临床结果的贡献。该项目对于识别新型分子靶点的功能性遗传变异以及开发新型临床诊断和预后工具具有重要意义。公共卫生相关性：囊性纤维化 (CF) 肺部疾病的特征是铜绿假单胞菌慢性感染，是 CF 患者发病和死亡的主要原因。由此产生的数据将定义调理抗体在粘液铜绿假单胞菌肺早期感染中的调理抗体的表达以及宿主反应对临床结果的贡献。该项目对于识别新分子靶点的功能性遗传变异以及开发新的临床诊断和预后工具具有重要意义。