A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects.
A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects.
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神经管缺陷中 5,10 亚甲基四氢叶酸还原酶的遗传缺陷。
DOI：
10.1093/oxfordjournals.qjmed.a069003
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
J. Scott
中科院分区：
文献类型：
--
作者：
A. Whitehead;Paula M. Gallagher;J. Mills;P. Kirke;H. Burke;A. Molloy;D. Weir;D. Shields;J. Scott
现在已经证实，围孕期服用叶酸可以降低神经管缺陷 (NTD) 的风险。最近的研究表明同型半胱氨酸代谢异常是一个关键因素。研究了 5,10 亚甲基四氢叶酸还原酶基因（一种在同型半胱氨酸代谢中重要的酶）与 NTD 的关系。为了确定不耐热形式的还原酶的等位基因频率，从 NTD 患者、NTD 患者的父母和正常对照中收集了 DNA 样本。在 82 名 NTD 患者中，有 15 人 (18.3%) 的异常耐热等位基因是纯合的。这显着高于（p = 0.01）对照人群 6.1% 的比率（比值比 3.47，95% CI 1.28-9.41）。这是在 NTD 中发现的第一个特定遗传异常。它解释了一些 NTD 与同型半胱氨酸升高之间的关联，因为还原酶在同型半胱氨酸代谢中很重要。它还解释了叶酸补充剂如何通过克服 5,10 亚甲基四氢叶酸转化为 5 甲基四氢叶酸的部分阻碍来预防某些 NTD。基因筛查可以识别需要补充叶酸的女性，以降低生育患有被忽视的热带疾病的风险。
It is now well-established that folic acid, taken peri-conceptionally, can reduce the risk of neural tube defects (NTDs). Recent work has demonstrated that an abnormality of homocysteine metabolism is a critical factor. The gene for 5,10 methylenetetrahydrofolate reductase, an enzyme important in homocysteine metabolism, was studied in relation to NTDs. To determine the frequency of the allele for the thermolabile form of the reductase, DNA samples were collected from people with NTDs, parents of people with NTDs, and normal controls. Of 82 people with NTDs, 15 (18.3%) were homozygous for the abnormal, thermolabile allele. This was significantly higher (p = 0.01) than the rate of 6.1% in the control population (odds ratio 3.47, 95% CI 1.28-9.41). This is the first specific genetic abnormality to be identified in NTDs. It explains the association between some NTDs and elevated homocysteine, given that the reductase is important in homocysteine metabolism. It also explains how folic acid supplementation prevents some NTDs, by overcoming a partial block in the conversion of 5,10 methylenetetrahydrofolate to 5 methyltetrahydrofolate. Genetic screening could identify women who will require folic acid supplements to reduce their risk of having a child with an NTD.