Environmental Determinants of Neural Tube Defects

神经管缺陷的环境决定因素

• 批准号: 6901623
• 负责人: LAURA E. MITCHELL
• 金额: $ 17.47万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6901623
• 关键词: China; arsenic; carbopolycyclic compound; clinical research; congenital nervous system disorder; diet; embryo /fetus toxicology; environmental exposure; epidemiology; gene environment interaction; genetic susceptibility; human subject; nutrition related tag

Neural tube defects (NTDs) are common, serious malformations that are associated with both excess morbidity and mortality. Although there are several known causes of NTDs, a specific etiologic agent(s) cannot be identified in the majority of cases. Maternal proximity to hazardous waste sites and exposure to pesticides have both been implicated as, but are not considered to be established risk factors for NTDs in offspring. Definitive conclusions regarding the association between these, and other environmental exposures and NTD risk have been hampered by the rarity of this outcome (<1/1000 births), differences in exposure assessment between studies, and overly simplistic etiological models. The studies proposed in this application are designed to minimize these limitations while addressing the primary study hypothesis: maternal exposure to polycyclic aromatic hydrocarbons and inorganic arsenic contributes to the risk of NTDs in offspring, and the effects of these environmental exposures are modified by nutritional and genetic factors. In our evaluation of this hypothesis we will consider the possibility that the interplay of environmental and genetic risk factors may be more relevant to the risk of NTDs than is the independent main effect of any single factor. In addition, we will consider both the maternal and the embryonic genotypes as potential modifiers of the association between maternal exposures and risk of NTDs in offspring.

神经管缺陷（NTDs）是常见的，严重的畸形，与过度的发病率和死亡率。虽然有几个已知的NTD的原因，一个特定的病原体（S）不能确定在大多数情况下。母亲接近危险废物场地和接触农药都被牵连，但不被认为是后代NTD的既定风险因素。关于这些和其他环境暴露与NTD风险之间的关联的连续性结论受到这种结果的罕见性（<1/1000出生），研究之间暴露评估的差异以及过于简单的病因学模型的阻碍。本申请中提出的研究旨在最大限度地减少这些限制，同时解决主要研究假设：母体暴露于多环芳烃和无机砷有助于后代NTD的风险，这些环境暴露的影响被营养和遗传因素所改变。在我们对这一假设的评估中，我们将考虑环境和遗传风险因素的相互作用可能比任何单一因素的独立主效应与NTD风险更相关的可能性。此外，我们将考虑母体和胚胎基因型作为母体暴露与后代NTD风险之间关联的潜在修饰因子。