Genetics of Infection and its Relationship with CVD Risk

感染遗传学及其与 CVD 风险的关系

• 批准号: 7143137
• 负责人: Harald Heinz Herbert Goring
• 金额: $ 44.52万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143137
• 关键词: Bacteroides gingivalis; Helicobacter; Herpes simplex disease; Herpesviridae disease; bacterial disease; cardiovascular disorder risk; chlamydial disease; clinical research; cytomegalovirus; disease /disorder etiology; family genetics; genetic mapping; genetic susceptibility; hepatitis A; human data; human herpesvirus 8; human tissue; inflammation; linkage mapping; virus diseases

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is a major public health concern in most human populations. While much research effort has been directed towards identifying the genetic and environmental factors that influence an individual's risk of CVD, the potential involvement of infectious agents in disease etiology has received comparatively little attention, despite substantial evidence that infections contribute to inflammation and elevate the risk of CVD-related morbidity and mortality. We propose to assess the role of genetic factors of the human host in regulating susceptibility to infection in a systematic manner by means of a large-scale family study. In preliminary work, we have shown that serological phenotypes indicative of infection with several common bacterial and viral pathogens are heritable. Furthermore, we have mapped a locus involved in regulating susceptibility to infection by Chlamydia pneumonias by genome-wide linkage analysis in Mexican American families. In this project, we will expand our research to encompass 7 common pathogens---Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, cytomegalovirus, hepatitis A virus, herpes simplex virus 1, and human herpesvirus 8---in a much larger pedigree sample of 2,500 Mexican Americans from San Antonio, TX. The 4 main goals of the project are to: 1) determine the phenotypic and genetic correlation of infection and inflammation; 2) assess the importance of host genes in regulating susceptibility to infection; 3) localize major genes involved in regulation of infection susceptibility in the human genome; and 4) identify the gene(s) and most likely functional variant(s) responsible for 2 significant linkage signals. This project takes advantage of 3 well-established family studies---the San Antonio Family Heart Study, the San Antonio Family Diabetes/Gallbladder Study, and the Veterans Administration Genetic Epidemiology Study. Genome-wide marker genotypes already exist in all 3 studies. In addition, a variety of CVD-related phenotypes, including inflammation markers, have already been measured. Serum and plasma samples from these studies are available for use in the proposed research. Relevance to Public Health: The proposed research is highly relevant to public health, given the potentially serious complications of infections with these pathogens and their likely contribution to CVD, which is a major contributor to morbidity and mortality in the US. Improved understanding of the genetic aspects of infection and its relationship with CVD risk may lead to novel strategies for prevention and treatment of infection and CVD.

描述（由申请人提供）：心血管疾病（CVD）在大多数人群中是一个主要的公共卫生问题。尽管许多研究工作旨在确定影响个人CVD风险的遗传和环境因素，但传染剂在疾病病因中的潜在参与却很少受到关注，尽管有大量证据表明感染会导致炎症并提高与CVD相关的发病率和死亡率的风险。我们建议通过大规模的家庭研究来评估人类宿主以系统的方式调节感染易感性的作用。在初步工作中，我们已经表明，表现出几种常见细菌和病毒病原体感染的血清原理表型是可以遗传的。此外，我们通过墨西哥裔美国家庭中的全基因组连锁分析来调节肺炎衣原体肺炎感染的易感性。 In this project, we will expand our research to encompass 7 common pathogens---Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, cytomegalovirus, hepatitis A virus, herpes simplex virus 1, and human herpesvirus 8---in a much larger pedigree sample of 2,500 Mexican Americans from San Antonio, TX.该项目的4个主要目标是：1）确定感染和炎症的表型和遗传相关性； 2）评估宿主基因在调节感染易感性方面的重要性； 3）将主要基因定位为调节人类基因组中的感染易感性； 4）确定负责2个重要链接信号的基因和最可能的功能变体。该项目利用了3项成熟的家庭研究---圣安东尼奥家庭心脏研究，圣安东尼奥家庭糖尿病/胆囊研究和退伍军人管理遗传流行病学研究。在所有3项研究中，全基因组标记基因型均已存在。此外，已经测量了各种CVD相关的表型，包括炎症标记。这些研究中的血清和血浆样品可用于拟议的研究。 与公共卫生有关：鉴于这些病原体的潜在严重并发症及其对CVD的可能贡献，这项研究可能与公共卫生高度相关，这是美国发病率和死亡率的主要贡献。对感染的遗传方面及其与CVD风险的关系有了改进的了解，可能会导致预防和治疗感染和CVD的新型策略。