NICHD HEALTH RESEARCH BOARD OF IRELAND NEURAL TUBE DEFECTS STUDY

流行病学分支正在与卫生研究委员会和爱尔兰的Trinity学院合作进行一些研究。 这些研究旨在确定叶酸降低神经管缺陷风险的生化机制。 在都柏林分娩的爱尔兰妇女中，有很大一部分人的数据和血液样本已经收集。正在研究的样本来自妊娠结束时分娩的神经管缺陷儿童的妇女和对照组妇女，其妊娠结束时分娩的正常儿童。还从有受影响儿童的家庭收集样本。 叶酸代谢和其他营养措施的各个方面正在研究中。 我们已经证明，在B12水平较低的情况下，携带NTD胎儿的妇女比携带正常胎儿的妇女具有显著较高的同型半胱氨酸水平。 我们还证明了一个负责消除同型半胱氨酸的异常基因也参与其中。 具体而言，基因缺陷产生所谓的5，10亚甲基四氢叶酸还原酶的热不稳定变体。 这种异常的酶在NTD患者中比正常人更常见。我们已经扩大了我们的调查，包括唇腭裂患者。 关于叶酸是否可以预防这些口腔裂缝，有相互矛盾的数据。 我们研究了裂缝和异常变异酶，热不稳定亚甲基四氢叶酸还原酶（MTHFR）之间的关系。在爱尔兰人群中，孤立性腭裂患者更有可能是这种酶的纯合子（TT）。因此，不能将叶酸转化为甲基形式可能是口腔裂的病因。

The Epidemiology Branch (DESPR) is conducting a number of studies in collaboration with the Health Research Board and Trinity College, Ireland. These investigations are designed to determine the biochemical mechanisms by which folate reduces the risk for neural tube defects. Data and blood samples have been collected on a large proportion of Irish women delivering babies in Dublin. Samples from women whose pregnancy ended in the delivery of a child with a neural tube defect and control women whose pregnancy ended in the delivery of a normal child are being studied. Samples are also being collected from families with an affected child. Various aspects of folate metabolism and other nutritional measures are being examined. We have demonstrated that at lower levels of B12, women carrying a fetus with an NTD have significantly higher levels of homocysteine than women carrying a normal fetus. We have also demonstrated that an abnormal gene responsible for elimination of homocysteine is involved. Specifically, a gene defect produces the so-called thermolabile variant of the 5,10 methylene tetrahydrofolate reductase enzyme. This abnormal enzyme is found significantly more frequently in individuals with NTDs than in normal individuals. We have expanded our investigation to include subjects with cleft lip and cleft palate. There are conflicting data on whether folic acid can prevent these oral clefts. We examined the relationship between clefts and the abnormal variant enzyme, thermolabile methylenetetrahydrofolate reductase (MTHFR). In the Irish population those with isolated cleft palates were significantly more likely to be homozygous (TT) for this enzyme. Thus, inability to convert folate to the methyl form may be an etiologic factor in oral clefts.