NICHD Health Research Board Of Ireland Neural Tube Defec

流行病学分部正在与健康研究委员会和爱尔兰都柏林三一学院合作进行一些出生缺陷研究。这些研究的主要目的是确定叶酸与出生缺陷之间的关系。到目前为止，研究的出生缺陷有神经管缺陷(NTDS)、口腔裂和唐氏综合症。这些研究集中在叶酸代谢领域的生化因素，以及与出生缺陷相关的叶酸相关基因的基因突变。在过去，我们已经证明，升高的同型半胱氨酸是NTDS的危险因素，亚甲基四氢叶酸还原酶(MTHFR)基因677C-和GT；T的突变是NTDS和口腔裂的危险因素，以及小剂量的叶酸(100-200微克)可以将红细胞叶酸提高到可以预防五分之一到近一半NTDS的水平。最近我们发现，每天补充100-200微克的叶酸可以显著降低同型半胱氨酸水平。这对预防NTD和可能预防心脏病和癌症都很重要。我们刚刚发现了一个与NTDS风险增加相关的新基因，该基因参与了四氢叶酸的相互转化。我们目前正在收集数据和样本，用于对口腔裂患者及其家人进行遗传分析，并收集先天性心脏病儿童和正常对照的样本。我们的遗传学研究目前集中在寻找与NTDS相关的叶酸酶基因变体。

The Epidemiology Branch is conducting a number of birth defect studies in collaboration with the Health Research Board and Trinity College, Dublin, Ireland. The main objective of these studies is to determine the relationship between folate and birth defects. The birth defects studied to date are neural tube defects (NTDs), oral clefts, and Down syndrome. These studies focus on biochemical factors in the area of folate metabolism, and on genetic mutations in folate related genes associated with birth defects. In the past we have shown that elevated homocysteine is a risk factor for NTDs, that a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene 677C->T is a risk factor for both NTDs and oral clefts, and that a small dose of folic acid (100-200 micrograms) can raise red cell folate to levels that can prevent a fifth to almost a half of NTDs. Recently we showed that folic acid supplementation with as little as 100-200 micrograms daily can reduce homocysteine significantly. This is important both for NTD prevention and possible prevention of heart disease and cancer. We have just identified a new gene associated with increased risk for NTDs, this gene is involved in interconversion of tetrahydrofolate. We are currently collecting data and samples for genetic analysis on subjects with oral clefts and their families and samples from children with congenital heart defects and normal controls.. Our genetic studies are currently focused on looking for folate enzyme gene variants that are associated with NTDs.