同型半胱氨酸临床应用的研究进展

同型半胱氨酸(homocysteine，Hcy)产生于必需氨基酸甲硫氨酸向半胱氨酸转化的过程，并通过甲基化作用参与脱氧核糖核酸(DNA)代谢。近年来诸多研究表明，血Hcy水平与多种疾病有直接或间接关系，如动脉硬化、心血管疾病、高血压、神经系统疾病、糖尿病、恶性肿瘤、妊娠期疾病、眼部疾病和骨质疏松等。人体血浆中Hcy的正常范围是5~15 μmol/L，＞15 μmol/L为高Hcy血症(hyper homocysteine, HHcy)。基因突变，叶酸、维生素B₆、B₁₂缺乏导致的营养不良及高甲硫氨酸的饮食模式均是Hcy升高的常见原因。研究证实，亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase, MTHFR)C677T基因多态性与血浆Hcy水平升高的易感性相关。而中国人群中MTHFR 677TT基因型表达显著高于其他种族。血清Hcy水平升高的致病机理可能为:促进炎症和血管钙化；脂质过氧化和抗氧化过程受损；刺激活性氧的产生，诱导氧化应激和血管功能障碍；内皮细胞毒性及功能障碍；抑制神经递质释放等。其他致病机制仍有待进一步研究。Hcy水平在预测疾病风险、控制疾病并发症、影响疾病转归中有重要价值。中国人口总体HHcy患病率较高，且地域差异显著。随着年龄增大，患病率也随之升高。Hcy水平监测有利于疾病的早发现、早诊断及严重并发症的早预防。结合最新文献报道，文章探讨Hcy致病机制及其与疾病的关系，为Hcy的临床应用提供参考。 

The clinical application value of homocysteine

Homocysteine (Hcy) is produced in the process of essential amino acid methionine to cysteine conversion, and participates in DNA metabolism through methylation. In recent years, many studies have shown that serum Hcy levels were directly or indirectly related to various diseases, such as arteriosclerosis, cardiovascular disease, hypertension, neurological disease, diabetes, cancer, pregnancy disease, eye disease and osteoporosis. The normal range of Hcy in human plasma is 5-15 μmol/L, and >15 μmol/L is hyper homocysteine (HHcy). Gene mutations, malnutrition caused by folic acid, vitamin B₆, and B₁₂ deficiency, and a high-methionine diet are common causes of elevated Hcy. Studies have confirmed that the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is associated with the susceptibility to elevated plasma Hcy levels, and the expression of the MTHFR 677TT genotype in the Chinese population is significantly higher than that of other races. The pathogenic mechanism of increased serum Hcy levels may be: promotion of inflammation and vascular calcification, impaired lipid peroxidation and antioxidant processes, stimulation of the production of reactive oxygen species, induction of oxidative stress and vascular dysfunction, endothelial cell toxicity and dysfunction, inhibit the release of neurotransmitters, and so on. Other pathogenic mechanisms still need to be further studied. The level of Hcy is important for the risk prediction of the disease, the controlling of the disease complications and the prognosis of the disease. The overall prevalence of HHcy in Chinese population is high, and the regional differences are significant. With the increase of age, the prevalence also increases. Monitoring of Hcy is conducive to early detection and diagnosis of diseases and prevention of serious complications. To provide reference for the clinical application of Hcy, this study comprehensively explores the relationship between Hcy and disease and its pathogenic mechanism on the basis of the latest literatures.