Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: Metabolic significance, risks and impact on folate requirement
Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: Metabolic significance, risks and impact on folate requirement
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DOI：
10.1093/jn/129.5.919
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发表时间：
1999-05-01
影响因子：
4.2
通讯作者：
Gregory, JF
中科院分区：
文献类型：
--
作者：
Bailey, LB;Gregory, JF
一种常见的遗传多态是由编码亚甲基四氢叶酸还原酶(MTHFR)的基因的C->；T替换引起的，MTHFR是产生同型半胱氨酸转化为蛋氨酸所需的5-甲基四氢叶酸(5-甲基-THF)的酶。在具有T/T基因(T/T)的个体中，功能代谢效应包括单碳叶酸衍生物的变化，血浆同型半胱氨酸的升高，以及与正常(C/C)或杂合(C/T)基因相比，补充叶酸的反应不同。当伴有叶酸缺乏时，与T/T基因相关的代谢变化被认为可以改变慢性疾病(如血管疾病和癌症)和神经管缺陷(NTD)的风险。增加叶酸摄入量对这些代谢异常的调节表明，受影响个体(T/T)的叶酸需求可能与正常(C/C)或杂合子(C/T)个体不同。这种常见的MTHFR基因多态与叶酸摄入量之间的复杂相互作用是密集研究的重点。
A common genetic polymorphism results from a C-->T substitution in the gene encoding methylenetetrahydrofolate reductase (MTHFR), the enzyme that produces 5-methyltetrahydrofolate (5-methyl-THF) required for the conversion of homocysteine to methionine. In individuals with the T/T genotype (T/T), functional metabolic effects include changes in one-carbon folate derivatives, elevations in plasma homocysteine and differences in response to folic acid supplementation compared with normal (C/C) or heterozygous (C/T) genotypes. The metabolic changes associated with the T/T genotype are postulated to modify risk for chronic disease (e.g., vascular disease and cancer) and neural tube defects (NTD) when accompanied by folate deficiency. The modulation of these metabolic abnormalities by increasing folate intake suggests that folate requirements may be different in affected individuals (T/T) relative to normal (C/C) or heterozygous (C/T) individuals. The complex interaction between this common genetic polymorphism of MTHFR and folate intake is the focus of intense investigation.