NICHD HEALTH RESEARCH BOARD OF IRELAND NEURAL TUBE DEFECTS STUDY

流行病学分部(DESPR)正在与卫生研究委员会和爱尔兰三一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。已经收集了很大比例的爱尔兰妇女在都柏林分娩的数据和血样。正在研究以神经管缺陷婴儿的分娩而终止妊娠的妇女和以正常婴儿的分娩结束妊娠的对照妇女的样本。还在从有受影响儿童的家庭中收集样本。正在研究叶酸新陈代谢的各个方面和其他营养措施。我们已经证明，在较低的B12水平下，怀有NTD的胎儿的同型半胱氨酸水平显著高于怀有正常胎儿的孕妇。我们还证明了一个负责消除同型半胱氨酸的异常基因参与其中。具体地说，基因缺陷会产生所谓的5，10亚甲基四氢叶酸还原酶的不耐热变体。这种异常的酶在NTDS患者中的发生率明显高于正常人。我们发表的一份报告显示，MTHFR的不耐热变体的存在与红细胞叶酸水平显著降低有关。另一篇论文表明，导致大多数同型半胱氨酸尿症的酶，胱硫氨酸合成酶，尽管与高同型半胱氨酸有关，但并不是神经管缺陷的重要原因。-叶酸、神经管缺陷、遗传学、口裂-人类受试者和人类受试者：仅采访、问卷或调查

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 published a report showing that the presence of the thermolabile variant of MTHFR is associated with significantly reduced levels of red cell folate. Another publication shows that the enzyme responsible for most cases of homocystinuria, cystathionine synthase, is not an important cause of neural tube defects despite its association with high homocysteine. - folic acid, neural tube defects, genetics, oral clefts - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only