Ou C Y, Stevenson R E, Brown V K, Schwartz C E, Allen W P, Khoury M J, Rozen R, Oakley G P, Adams M J
Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
Am J Med Genet. 1996 Jun 28;63(4):610-4. doi: 10.1002/(SICI)1096-8628(19960628)63:4<610::AID-AJMG15>3.0.CO;2-L.
Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.
具有热不稳定形式的5,10-亚甲基四氢叶酸还原酶（MTHFR）的人酶活性降低，血浆同型半胱氨酸增加，补充叶酸可降低其水平。最近发现该酶的热不稳定性是由MTHFR基因中的常见突变（677C→T）引起的。我们研究了41例神经管缺陷（NTD）胎儿的成纤维细胞培养物，并将其基因型与普通人群中109份血液样本的基因型进行了比较。677C→T纯合性与NTD风险增加7.2倍相关（95%置信区间：1.8 - 30.3；p值：0.001）。这些初步数据表明，MTHFR基因的677C→T多态性是脊柱裂和无脑儿的危险因素，这可能为叶酸预防这些类型的NTD提供部分生物学解释。
