Student Scientific Association "Farmakon", Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha St., 02-097 Warsaw, Poland.
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211 Warsaw, Poland.
Int J Mol Sci. 2023 Dec 22;25(1):193. doi: 10.3390/ijms25010193.
Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the one-carbon cycle. This enzyme is essential for the metabolism of methionine, folate, and RNA, as well as for the production of proteins, DNA, and RNA. MTHFR catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to its active form, 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Numerous variants of the gene have been recognised, among which the C677T variant is the most extensively studied. The C677T polymorphism, which results in the conversion of valine to alanine at codon 222, is associated with reduced activity and an increased thermolability of the enzyme. Impaired MTHFR efficiency is associated with increased levels of homocysteine, which can contribute to increased production of reactive oxygen species and the development of oxidative stress. Homocysteine is acknowledged as an independent risk factor for cardiovascular disease, while chronic inflammation serves as the common underlying factor among these issues. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and an increased risk of cardiovascular disease, hypertension, diabetes, and overweight/obesity. There is substantial evidence supporting this association, although several studies have concluded that the polymorphism cannot be reliably used for prediction. This review examines the latest research on polymorphisms and their correlation with cardiovascular disease, obesity, and epigenetic regulation.
亚甲基四氢叶酸还原酶（MTHFR）是一碳循环中的关键调节酶。这种酶对于蛋氨酸、叶酸和 RNA 的代谢，以及蛋白质、DNA 和 RNA 的产生是必不可少的。MTHFR 催化 5,10-亚甲基四氢叶酸不可逆地转化为其活性形式 5-甲基四氢叶酸，后者是同型半胱氨酸重新甲基化为蛋氨酸的辅助底物。已经识别出该基因的许多变体，其中 C677T 变体是研究最多的。C677T 多态性导致密码子 222 处缬氨酸转换为丙氨酸，与酶活性降低和热稳定性增加有关。MTHFR 效率受损与同型半胱氨酸水平升高有关，同型半胱氨酸可导致活性氧产生增加和氧化应激发展。同型半胱氨酸被认为是心血管疾病的独立危险因素，而慢性炎症是这些问题的共同潜在因素。许多研究已经确定了 C677T 多态性与心血管疾病、高血压、糖尿病和超重/肥胖风险增加之间是否存在关联。有大量证据支持这种关联，尽管一些研究得出结论认为该多态性不能可靠地用于预测。本综述考察了关于 MTHFR 多态性及其与心血管疾病、肥胖和表观遗传调控相关性的最新研究。
