NICHD Health Research Board Of Ireland Neural Tube Defec

流行病学分支正在与健康研究委员会和爱尔兰都柏林的Trinity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和出生缺陷之间的关系。迄今为止研究的出生缺陷有神经管缺陷、口裂、先天性心脏缺陷、唐氏综合征和脐膨出。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，我们已经表明，高同型半胱氨酸是NTDs的危险因素，亚甲基四氢叶酸还原酶（MTHFR）基因677 C->T突变是NTDs的危险因素，小剂量的叶酸（100-200微克）可以提高红细胞叶酸水平，可以预防五分之一到几乎一半的NTDs。我们已经表明，亚甲基四氢叶酸还原酶（MTHFD），一个重要的基因在生产嘌呤和嘧啶的DNA合成的NTDs的危险因素。携带该基因R653 Q变体的母亲生下NTD的风险增加。 在过去的一年里，我们扩大了我们在MTHFD方面的工作，表明R653 Q变异是严重胎盘早剥和不明原因的中期妊娠丢失的风险因素。我们还发表了一份报告，显示NTDs的一个重要基因风险因子MTHFR C677 T也是脐膨出的一个风险因子。我们已经探索了其他被认为是NTD风险因素的基因，表明它们在我们大量遗传同质的爱尔兰家庭中不是风险因素。

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.