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。 在过去的一年里，我们扩大了对MTHFD的研究，表明R653Q变异是严重胎盘早剥和不明原因中期妊娠丢失的危险因素。我们还发表了一份报告，表明NTDS的一个重要基因风险因素MTHFR C677T也是脐膨出的风险因素。我们已经探索了其他被认为是NTDS危险因素的基因，表明在我们大量遗传同质的爱尔兰家庭中，这些基因不是危险因素。

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 past year, we have expanded our work on MTHFD, showing that the R653Q variant is a risk factor for severe abruptio placentae and for unexplained second trimester pregnancy loss. We have also published a report showing that an important gene risk factor for NTDs, MTHFR C677T, is also a risk factor for omphalocele. We have explored other genes that have been proposed to be risk factors for NTDs, showing that they are not risk factors in our large population of genetically homogeneous Irish families.