Vitamin D and Food Allergy: a Prospective Birth Cohort Study

描述(申请人提供)：食物过敏(FA)，定义为免疫球蛋白(Ig)E介导的对食物的超敏反应，在美国和世界范围内是一个日益严重的临床和公共卫生问题。鉴于维生素D缺乏在美国人群中普遍存在，其流行病学和地理模式与变态反应性疾病的流行几乎平行，以及它在免疫反应调节中的公认作用，维生素D缺乏在FA的发展中的作用引起了极大的兴趣。到目前为止，还没有研究评估维生素D缺乏对FA发生的影响，也没有研究评估基因与维生素D的相互作用。这项建议的中心焦点是利用波士顿医学中心(BMC)出生队列的广泛资源，调查脐带血25(OH)D浓度是否与FA的发展相关，以及这种相关性是否可以通过个体基因变异来改变。这一队列由在BMC登记或正在登记的约9000对母婴组成。在最初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产妇和脐带血样本。这一队列从出生起就被跟踪，以确定FA和其他过敏性疾病的事件病例。在出生后的随访中收集的信息包括FA问卷；包括医生诊断ICD代码的医疗记录；儿童的静脉血样；以及总的和食物和航空过敏原特异性的IgE。将进行嵌套病例对照研究，包括400例FA事件病例和800例从BMC出生队列中确定的无症状和非致敏对照。将实现两个主要目标：(1)评估脐血血浆(CBP)25(OH)D浓度与FA发展的关系，并调整潜在的重要产前和出生后混杂因素。(2)通过对重要协变量、群体混合和多重检验的调整，评估基因-维生素D交互作用对FA发生的影响。这项研究将集中在以下基因/区域的所有潜在功能SNPs：(1)。从FA(R56 AI080627)的全基因组关联研究中鉴定；(2)。从FA(R21 AI079872)的候选基因研究中进行鉴定；将通过独创性路径分析产生上述识别的基因；和(4)。已知参与25(OH)D代谢和调节途径。这一建议通过以下方式得到加强：使用现有的大型出生队列；通过将个体遗传易感性与评估维生素D状况的客观生物标记物相结合的创新方法；确保足够的统计能力的大样本量；以及高度互动和经验丰富的研究团队。这项研究的结果不仅将有助于建立低维生素D与新生儿发育FA之间的因果关系，而且还将增强识别低维生素D影响的遗传易感性新生儿的能力。最终，这将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。 食物过敏(FA)在美国和世界范围内是一个主要的临床和公共卫生问题；也是导致过敏反应的最常见的急诊室原因。早期低维生素D水平可能是FA发生的危险因素之一。这项建议的主要焦点是帮助我们了解脐带血维生素D浓度是否与FA相关，以及这种相关性是否可以被以前从未研究过的单个基因变异所改变。

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.