FUT2 Genotype Impact on National Burden of Norovirus Infections

FUT2 基因型对国家诺如病毒感染负担的影响

• 批准号: 8645066
• 负责人: Rebecca Lynn Currier Curran
• 金额: $ 4.48万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-11 至 2017-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645066
• 关键词: Acute; Address; Adult; Age; American; Binding; Blood Group Antigens; Campylobacter jejuni; Carbohydrates; Case Study; Case-Control Studies; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical Data; Collaborations; Communicable Diseases; Country; DNA; Day center care; Development; Diarrhea; Disease Outbreaks; Disease Resistance; Dose; Enrollment; Enzymes; Epidemiologist; Epidemiology; Epithelial; Escherichia coli; FUT2 gene; Feces; Fellowship; Future; Gastroenteritis; General Population; Genes; Genetic; Genotype; Germ; Goals; Household; Human; Human Resources; In Vitro; Incidence; Individual; Infection; Infectious Disease Epidemiology; Institution; Intestines; Investigation; Literature; Long-Term Care; Medical; Mentors; Military Personnel; Molecular; Mutation; Nonsense Mutation; Norovirus; Pattern; Physicians; Population; Predisposition; Production; Public Health; Publishing; Research; Research Personnel; Research Training; Resistance; Risk; Rotavirus; Rotavirus Vaccines; Saliva; Scientist; Shipping; Ships; Specificity; Surface; Techniques; Testing; Therapeutic; Time; Training; Vaccination; Vaccines; Virus; Virus Shedding; Visit; Work; base; career; clinical practice; design; disorder prevention; foodborne illness; genetic variant; meetings; member; multidisciplinary; national surveillance; novel; novel vaccines; pathogen; population based; public health relevance; risk variant; sugar; surveillance network

DESCRIPTION (provided by applicant): By age five, 1 in 6 U.S. children have had a case of medically attended norovirus acute gastroenteritis (AGE). Norovirus is the leading cause of U.S. pediatric AGE, with reported cases rising 52% in 2012 due to the emergence of a novel strain. The purpose of this study is to determine the contribution of the FUT2 (secretor) gene to the population burden of pediatric AGE, particularly norovirus-associated AGE. The FUT2 gene enzyme controls the production of certain sugars at the gut surface, and is hypothesized to be involved in AGE pathogen susceptibility by modifying the surface where AGE pathogens first interact with the host. Noroviruses in particular bind to the sugars synthesized by FUT2 gene enzymes. Nearly 25% of the U.S. population lacks a functional FUT2 gene; these individuals are known as "non- secretors." Several challenge studies and outbreak investigations have shown that non-secretors are resistant to infection by certain strains of noroviruses. However, this association does not hold for all strains, and no studies to date have explored the impact of this genetic variant on population-wide patterns of norovirus AGE. Additionally, few studies have explored the extent to which non-secretors may still shed the virus- thus potentially infecting others- even if they are protected from symptomatic infection by certain strains. The proposed research tests the central hypothesis that secretor genetics determines the population risk of norovirus symptomatic infection and asymptomatic shedding as well as overall AGE susceptibility. For this study, active AGE surveillance was conducted at six pediatric institutions across the country in affiliation with the New Vaccine Surveillance Network (NVSN) of the Centers for Disease Control and Prevention (CDC). Stool (for pathogen testing) and saliva (for DNA genotyping) were collected from 1505 AGE cases and 827 healthy control children under the age of five from December 2011- November 2012. Projections based on preliminary analyses show that at least 300 of these cases will be norovirus positive, including a significant number of cases infected by the 2012 emerging norovirus strain. The proposed research has two specific aims: (1) Determine the association between FUT2 (secretor) genotype and risk of pediatric AGE detected through a national surveillance network and (2) Compare asymptomatic shedding of norovirus in secretors vs. non-secretors. This work has direct

描述(由申请人提供)：到5岁时，每6名美国儿童中就有1名患有诺沃克病毒急性胃肠炎(AGE)。诺沃克病毒是美国儿童老龄化的主要原因，由于一种新毒株的出现，2012年报告的病例增加了52%。本研究的目的是确定FUT2(分泌物)基因对儿童年龄，特别是诺如病毒相关年龄的人口负担的贡献。FUT2基因酶控制肠道表面某些糖的产生，并被认为通过改变AGE病原体与宿主首次相互作用的表面而参与AGE病原体的易感性。诺如病毒尤其与FUT2基因酶合成的糖结合。近25%的美国人缺乏功能性的FUT2基因；这些人被称为“非分泌者”。一些挑战研究和暴发调查表明，非分泌者对某些诺如病毒株的感染具有抵抗力。然而，这种联系并不适用于所有的毒株，到目前为止，还没有研究探索这种遗传变异对诺沃克病毒年龄的全人群模式的影响。此外，很少有研究探索非分泌型病毒仍然可能在多大程度上传播病毒--从而潜在地感染其他人--即使他们受到保护，不会受到某些菌株的症状感染。这项拟议的研究测试了中心假设，即分泌器遗传学决定了诺沃克病毒症状性感染和无症状脱落的人群风险以及总体年龄易感性。在这项研究中，对六个儿科机构进行了积极的年龄监测。 在全国范围内与疾病控制和预防中心(CDC)的新疫苗监测网络(NVSN)建立联系。粪便(用于病原体检测)和唾液(用于DNA基因分型)收集自2011年12月至2012年11月期间的1505例5岁以下儿童和827名5岁以下健康对照儿童。基于初步分析的预测显示，其中至少300例将是诺沃克病毒阳性，包括相当数量的感染2012年新出现的诺沃克病毒株的病例。这项拟议的研究有两个具体目标：(1)确定通过国家监测网络检测到的FUT2(分泌物)基因与儿童年龄风险的关联；(2)比较分泌者和非分泌者中诺沃克病毒的无症状脱落。这项工作具有直接性