NICHD HEALTH RESEARCH BOARD OF IRELAND NEURAL TUBE DEFECTS STUDY

流行病学处正在与卫生研究委员会和爱尔兰三一学院合作开展若干研究。这些研究旨在确定叶酸降低神经管缺陷风险的生化机制。数据和血液样本已经收集了很大一部分在都柏林分娩的爱尔兰妇女。研究人员从妊娠结束后产下神经管缺陷婴儿的妇女和妊娠结束后产下正常婴儿的对照组妇女中抽取样本。还从有受感染儿童的家庭收集样本。正在研究叶酸代谢和其他营养措施的各个方面。我们已经证明，在维生素B12水平较低的情况下，怀NTD胎儿的妇女同型半胱氨酸水平明显高于怀正常胎儿的妇女。我们还证明了一种负责消除同型半胱氨酸的异常基因参与其中。具体来说，一种基因缺陷会产生所谓的5,10亚甲基四氢叶酸还原酶的耐热性变异。这种异常酶在ntd患者中比在正常人群中更为常见。我们已经扩大了我们的研究对象，包括唇裂和腭裂。关于叶酸是否能预防这些唇裂，有相互矛盾的数据。我们研究了裂缝与异常变异酶，耐热性亚甲基四氢叶酸还原酶（MTHFR）之间的关系。在爱尔兰人群中，那些与分离腭裂明显更可能是纯合子（TT）的这种酶。因此，不能将叶酸转化为甲基可能是唇裂的一个病因。

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.