Vitamin D and Food Allergy: a Prospective Birth Cohort Study

维生素 D 和食物过敏：前瞻性出生队列研究

• 批准号: 7874959
• 负责人: Xin Liu
• 金额: $ 18.38万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7874959
• 关键词: Accident and Emergency department; Admixture; Allergens; Allergic Disease; Anaphylaxis; Biological Markers; Birth; Blood specimen; Boston; Candidate Disease Gene; Child; Childhood; Clinical; Code; Cohort Studies; Complement; Data; Data Collection; Databases; Development; Diagnosis; Enrollment; Epidemiology; Etiology; Evidence based intervention; Food; Food Hypersensitivity; Funding; Future; Genes; Genetic Predisposition to Disease; Goals; Heterogeneity; Hypersensitivity; IgE; Immune; Immune response; Immunoglobulins; Incidence; Individual; Infant; International Classification of Disease Codes; Intervention; Investigation; Laboratories; Lead; Life; Mediating; Medical Records; Medical center; Metabolism; Mothers; Nested Case-Control Study; Newborn Infant; Pathway Analysis; Pattern; Physicians; Plasma; Population; Prevalence; Public Health; Questionnaires; Reaction; Regulation; Regulatory Pathway; Research; Research Infrastructure; Resources; Risk Factors; Role; Sample Size; Sampling; Severities; Single Nucleotide Polymorphism; Subgroup; Testing; Umbilical Cord Blood; Venous blood sampling; Visit; Vitamin D; Vitamin D Deficiency; case control; cohort; computing resources; cost; cost effective; design; experience; follow-up; genetic variant; genome wide association study; innovation; interest; postnatal; prenatal; prevent; prospective

DESCRIPTION (provided by applicant): Food allergy (FA), defined as an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, is a growing clinical and public health problem in the U.S. and worldwide. The role of vitamin D deficiency in the development of FA is of great interest, given widespread vitamin D deficiency in the U.S. population, its nearly parallel epidemiological and geographic patterns with the prevalence of allergic diseases, and its recognized role in regulation of immune responses. To date, no study has been conducted to evaluate the effects of vitamin D deficiency on the development of FA, nor gene-vitamin D interactions. The central focus of this proposal is to investigate whether cord blood 25(OH)D concentrations are associated with the development of FA, and whether such associations can be modified by individual genetic variants, using the extensive resources of the Boston Medical Center (BMC) Birth Cohort. This cohort consists of ~9,000 mother-infant pairs enrolled or being enrolled at the BMC. The information collected at the initial recruitment includes comprehensive pre- and peri-natal epidemiological and clinical variables along with maternal and cord blood samples. This cohort has been followed from birth onward to identify incident cases of FA and other allergic diseases. The information collected at postnatal follow-ups includes FA questionnaires; medical records including ICD codes of physician diagnosis; child's venous blood sample; and total and food- and aero- allergen-specific IgE. A nested case-control study will be conducted, including 400 FA incident cases and 800 asymptomatic and non-sensitized controls identified from the BMC Birth Cohort. Two primary aims will be accomplished: (1) To assess the association of cord blood plasma (CBP) 25(OH)D concentration with the development of FA with adjustment for potentially important prenatal and postnatal confounders. (2) To assess the gene-vitamin D interaction effects on the development of FA, with adjustment for important covariates, population admixture, and multiple testing. This study will focus on all potentially functional SNPs in the following genes/regions: (1). To be identified from genome-wide association study (GWAS) of FA (R56 AI080627); (2). To be identified from candidate gene study of FA (R21 AI079872); (3). To be generated by Ingenuity Pathway Analysis given the above identified genes; and (4). Known to be involved in 25(OH)D metabolism and regulatory pathways. This proposal is strengthened by: using a large, existing birth cohort; an innovative approach by integrating individual genetic susceptibility with an objective biomarker for assessing vitamin D status; a large sample size that assures adequate statistical power; and a highly interactive and experienced research team. The findings from this study will not only help establish causal relationship between low vitamin D and development FA in newborns, but will also enhance the ability to identify newborns who are genetically susceptible to the effect of low vitamin D. Ultimately, this can lead to design targeted, cost- effective clinical and public health interventions with the goal of preventing or reducing the incidence of FA. Food allergy (FA) is a major clinical and public health problem in the US and worldwide; and is also the most common cause of emergency room visits for anaphylaxis. Low vitamin D level in early life may be one of the risk factors for the development of FA. The main focus of this proposal is to help us understand if cord blood vitamin D concentrations are associated with FA and if such associations can be modified by individual genetic variants, which has never been investigated before.

描述（由申请人提供）：食物过敏 (FA) 被定义为免疫球蛋白 (Ig) E 介导的对食物的过敏反应，是美国和全世界日益严重的临床和公共卫生问题。鉴于维生素 D 缺乏在美国人群中广泛存在、其流行病学和地理模式与过敏性疾病的流行几乎平行，以及其在免疫反应调节中的公认作用，维生素 D 缺乏在 FA 发展中的作用引起了人们的极大兴趣。迄今为止，尚无研究评估维生素 D 缺乏对 FA 发育的影响，也没有评估基因与维生素 D 相互作用的影响。该提案的核心重点是利用波士顿医学中心 (BMC) 出生队列的广泛资源，研究脐带血 25(OH)D 浓度是否与 FA 的发生相关，以及这种关联是否可以通过个体遗传变异来改变。该队列由大约 9,000 对在 BMC 注册或正在注册的母婴组成。初次招募时收集的信息包括全面的产前和围产期流行病学和临床变量以及母体和脐带血样本。该队列从出生起就被追踪，以识别 FA 和其他过敏性疾病的病例。产后随访收集的信息包括 FA 问卷；医疗记录，包括医生诊断的 ICD 代码；儿童的静脉血样本；以及食物和空气过敏原特异性 IgE 总量。将进行一项巢式病例对照研究，包括从 BMC 出生队列中确定的 400 例 FA 事件病例和 800 例无症状和非致敏对照。将实现两个主要目标：(1) 评估脐带血血浆 (CBP) 25(OH)D 浓度与 FA 发展的关系，并调整潜在重要的产前和产后混杂因素。 (2) 评估基因-维生素 D 相互作用对 FA 发展的影响，并对重要协变量、群体混合和多重测试进行调整。这项研究将重点关注以下基因/区域中所有潜在的功能性 SNP：(1)。从 FA (R56 AI080627) 的全基因组关联研究 (GWAS) 中鉴定； （2）。从FA候选基因研究中鉴定（R21 AI079872）； （3）。根据上述确定的基因，通过 Ingenuity Pathway Analysis 生成；和（4）。已知参与 25(OH)D 代谢和调节途径。该提案通过以下方式得到加强： 使用大量现有的出生队列；一种创新方法，将个体遗传易感性与评估维生素 D 状态的客观生物标志物相结合；确保足够的统计功效的大样本量；以及一支高度互动且经验丰富的研究团队。这项研究的结果不仅有助于建立新生儿低维生素 D 与发育性 FA 之间的因果关系，而且还将增强识别在遗传上易受低维生素 D 影响的新生儿的能力。最终，这可以导致设计有针对性的、具有成本效益的临床和公共卫生干预措施，以预防或减少 FA 的发生率。 食物过敏（FA）是美国和全世界的一个主要临床和公共卫生问题；这也是因过敏反应而去急诊室的最常见原因。生命早期维生素 D 水平低可能是发生 FA 的危险因素之一。该提案的主要重点是帮助我们了解脐带血维生素 D 浓度是否与 FA 相关，以及这种关联是否可以通过个体遗传变异来改变，而这在之前从未被研究过。