McNulty Helene, McKinley Michelle C, Wilson Barbara, McPartlin Joseph, Strain J J, Weir Donald G, Scott John M
Northern Ireland Centre for Diet and Health, University of Ulster, Coleraine, United Kingdom.
Am J Clin Nutr. 2002 Aug;76(2):436-41. doi: 10.1093/ajcn/76.2.436.
Methylenetetrahydrofolate reductase (MTHFR; EC 1.7.99.5) supplies the folate needed for the metabolism of homocysteine. A reduction in MTHFR activity, as occurs in the homozygous state for the 677C-->T (so-called thermolabile) enzyme variant (TT genotype), is associated with an increase in plasma total homocysteine (tHcy).
In vitro studies suggest that the reduced activity of thermolabile MTHFR is due to the inappropriate loss of its riboflavin cofactor. We investigated the hypothesis that MTHFR activity in the TT genotype group is particularly sensitive to riboflavin status.
We studied tHcy and relevant B-vitamin status by MTHFR genotype in a cross-sectional study of 286 healthy subjects aged 19-63 y (median: 27 y). The effect of riboflavin status was examined by dividing the sample into tertiles of erythrocyte glutathionine reductase activation coefficient, a functional index of riboflavin status.
Lower red blood cell folate (P = 0.0001) and higher tHcy (P = 0.0082) concentrations were found in the TT group than in the heterozygous (CT) or wild-type (CC) groups. However, these expected relations in the total sample were driven by the TT group with the lowest riboflavin status, whose mean tHcy concentration (18.09 micromol/L) was almost twice that of the CC or CT group. By contrast, adequate riboflavin status rendered the TT group neutral with respect to tHcy metabolism.
The high tHcy concentration typically associated with homozygosity for the 677C-->T variant of MTHFR occurs only with poor riboflavin status. This may have important implications for governments considering new fortification policies aimed at the prevention of diseases for which this genotype is associated with increased risk.
亚甲基四氢叶酸还原酶（MTHFR；EC 1.7.99.5）为同型半胱氨酸代谢提供所需的叶酸。MTHFR活性降低，如在677C→T（所谓的热不稳定）酶变体的纯合状态（TT基因型）中出现的情况，与血浆总同型半胱氨酸（tHcy）升高有关。
体外研究表明，热不稳定MTHFR活性降低是由于其核黄素辅因子的不适当丧失。我们研究了以下假设：TT基因型组中的MTHFR活性对核黄素状态特别敏感。
我们在一项对286名年龄在19至63岁（中位数：27岁）的健康受试者的横断面研究中，按MTHFR基因型研究了tHcy和相关B族维生素状态。通过将样本分为红细胞谷胱甘肽还原酶激活系数（核黄素状态的功能指标）的三分位数来检查核黄素状态的影响。
与杂合子（CT）或野生型（CC）组相比，TT组的红细胞叶酸浓度较低（P = 0.0001），tHcy浓度较高（P = 0.0082）。然而，总样本中的这些预期关系是由核黄素状态最低的TT组驱动的，其平均tHcy浓度（18.09微摩尔/升）几乎是CC或CT组的两倍。相比之下，充足的核黄素状态使TT组在tHcy代谢方面呈中性。
通常与MTHFR的677C→T变体纯合性相关的高tHcy浓度仅在核黄素状态不佳时出现。这可能对考虑制定旨在预防该基因型与风险增加相关疾病的新强化政策的政府具有重要意义。
