Liew Siaw-Cheok, Gupta Esha Das
Department of Clinical Skills and Simulation Centre, International Medical University, Kuala Lumpur, Malaysia.
Department of Internal Medicine, International Medical University, Seremban, Malaysia.
Eur J Med Genet. 2015 Jan;58(1):1-10. doi: 10.1016/j.ejmg.2014.10.004. Epub 2014 Nov 4.
The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.
亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性与多种疾病（血管疾病、癌症、神经疾病、糖尿病、银屑病等）相关，C677T基因多态性的流行病学情况因地域和种族而异。5,10-亚甲基四氢叶酸还原酶（MTHFR）基因座定位于1号染色体短臂末端（1p36.6）。该酶对叶酸代谢很重要，而叶酸代谢是DNA、RNA和蛋白质甲基化过程中细胞代谢不可或缺的一部分。导致C677T基因多态性的MTHFR基因突变位于第4外显子，导致第222密码子处缬氨酸转变为丙氨酸，这是一种常见的基因多态性，会降低该酶的活性。与正常的非突变对照相比，纯合突变个体的同型半胱氨酸水平较高，杂合突变个体的同型半胱氨酸水平略有升高。高同型半胱氨酸血症是各种心血管疾病新出现的一个危险因素，鉴于这种基因多态性对患者发病率和死亡率的影响日益显著，作为未来健康教育的一部分，采取进一步的预防策略以及补充维生素B12和叶酸以降低血浆同型半胱氨酸水平的营养建议将是必要的。因此，这篇文献综述聚焦于近期全球范围内关于MTHFR C677T基因多态性与各种疾病关联的循证报告。
