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）是大多数人群的主要公共卫生问题。尽管大量研究工作致力于确定影响个体心血管疾病风险的遗传和环境因素，但感染因子在疾病病因学中的潜在参与相对较少受到关注，尽管有大量证据表明感染会导致炎症并增加心血管疾病的风险。 CVD 相关的发病率和死亡率。我们建议通过大规模的家庭研究，系统地评估人类宿主的遗传因素在调节感染易感性中的作用。在初步工作中，我们已经证明，表明几种常见细菌和病毒病原体感染的血清学表型是可遗传的。此外，我们通过墨西哥裔美国人家庭的全基因组连锁分析，绘制了一个参与调节肺炎衣原体感染易感性的基因座。在这个项目中，我们将在更大的谱系样本中扩大研究范围，涵盖 7 种常见病原体——肺炎衣原体、幽门螺杆菌、牙龈卟啉单胞菌、巨细胞病毒、甲型肝炎病毒、单纯疱疹病毒 1 型和人类疱疹病毒 8 型来自德克萨斯州圣安东尼奥市的 2,500 名墨西哥裔美国人。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）定位人类基因组中参与感染易感性调节的主要基因； 4) 鉴定负责 2 个显着连锁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局遗传流行病学研究。所有 3 项研究中均已存在全基因组标记基因型。此外，还测量了多种CVD相关表型，包括炎症标志物。这些研究中的血清和血浆样本可用于拟议的研究。 与公共卫生的相关性：考虑到这些病原体感染可能导致严重的并发症及其可能导致心血管疾病（心血管疾病是美国发病率和死亡率的主要原因），拟议的研究与公共卫生高度相关。更好地了解感染的遗传因素及其与 CVD 风险的关系可能会带来预防和治疗感染和 CVD 的新策略。