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，研究的出生缺陷包括神经管缺陷(NTDS)、口腔裂、先天性心脏缺陷、唐氏综合症和脐膨出。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-gt；T的突变是NTDS的危险因素，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。我们已经证明，亚甲基四氢叶酸还原酶(MTHFD)是一种重要的基因，它在合成DNA的嘌呤和嘧啶的过程中是NTDS的危险因素。携带该基因R653Q变异的母亲生下患有NTD的孩子的风险增加。这是第一个被证明是NTDS风险因素的母体基因。最近，我们发表了一份报告，表明MTHFR C677T不仅是纯合子状态的危险因素，而且在杂合子状态下也是危险因素。这一点很重要，因为超过50%的人至少有一个C677T变种的副本。 我们已经完成了对口腔裂患者及其家人的遗传分析的数据和样本收集，以及来自先天性心脏病儿童和正常对照的样本。我们的样本来自900多名唇腭裂患者和2000多名先天性心脏病儿童。将对这些受试者进行研究，以确定叶酸相关基因是否在先天性心脏病和先天性心脏病中具有重要的病因学意义。我们还收集并分析了25名无染色体缺陷的脐膨出儿童的DNA，并正在调查与候选基因的可能关系。

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, congenital heart defects,Down syndrome and omphalocele. 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 NTDs, 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. We have shown that methylenetetrahydrofolate reductase (MTHFD), an important gene in the production of purine and pyrimidine for DNA synthesis in a risk factor for NTDs. Mothers who have the R653Q variant of this gene are at increased risk of having a child with an NTD. This is the first maternal gene to be shown to be a risk factor for NTDs. Recently, we published a report showing that MTHFR C677T is not only a risk factor in the homozygous, but in the heterozygous state as well. This is important because over 50% of the population has a least one copy of the C677T variant. We have completed data and sample collection for genetic analysis on subjects with oral clefts and their families and samples from children with congenital heart defects and normal controls. We have samples from over 900 subjects with cleft lip or palate and from over 2000 children with congenital heart defects. These subjects will be studied to determine whether folate-related genes are etiologically important in clefts and congenital heart defects. We have also collected and analyzed DNA from 25 children with omphalocele who do not have chromosomal defects and are investigating possible relationships with candidate genes.