van der Put N M, Blom H J
Department of Pediatrics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Eur J Obstet Gynecol Reprod Biol. 2000 Sep;92(1):57-61. doi: 10.1016/s0301-2115(00)00426-7.
Folate administration substantially reduces the risk on neural tube defects (NTD). The interest for a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hcy levels in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate dependent Hcy metabolism. This leads to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with an increased risk of NTD and cause elevated Hcy concentrations. These levels can be normalized by an additional folate intake. Thus, a dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies, and also in part the protective effect of folate on NTD. Although, the MTHFR polymorphisms are only moderate risk factors, population wide they may account for an important part of the observed NTD prevalence.
叶酸补充可显著降低神经管缺陷（NTD）的风险。神经管缺陷患儿母亲血液中同型半胱氨酸（Hcy）水平升高的观察结果，引发了人们对与神经管缺陷相关的Hcy代谢紊乱的关注。这一观察结果促使人们对参与叶酸依赖性Hcy代谢的酶进行研究。这进而导致了首个以及可能第二个神经管缺陷遗传风险因素的发现。亚甲基四氢叶酸还原酶（MTHFR）基因中的C677T和A1298C突变与神经管缺陷风险增加相关，并导致Hcy浓度升高。额外摄入叶酸可使这些水平恢复正常。因此，MTHFR功能失调部分解释了神经管缺陷妊娠女性中观察到的Hcy水平升高现象，也部分解释了叶酸对神经管缺陷的保护作用。尽管MTHFR基因多态性只是中度风险因素，但在整个人口中，它们可能占观察到的神经管缺陷患病率的重要部分。
