亚甲基四氢叶酸还原酶基因C677T多肽性快速检测系统的建立

发布时间：2018-02-04 12:24

本文关键词： 亚甲基四氢叶酸还原酶基因分型单核苷酸多态性同型半胱氨酸荧光偏振　出处：《第四军医大学》2005年硕士论文　论文类型：学位论文

【摘要】：同型半胱氨酸(Homocysteine,Hcy)是转甲基和转硫基代谢过程中产生的一种氨基酸,血浆Hcy增高增加多种疾病危险性,包括血管病、冠心病、血栓形成、中风、神经管发育不全及糖尿病肾病等。亚甲基四氢叶酸还原酶(MTHFR)是Hcy代谢的一个关键酶,MTHFR可催化5,10—亚甲基四氢叶酸还原成5—甲基四氢叶酸的不可逆反应。MTHFR基因最常见多态性为677位核苷酸C→T置换(C677T),使酶活性区的丙氨酸(Ala)置换为缬氨酸(Val)生成不耐热酶,妨碍5—甲基四氢叶酸的合成,后者为Hcy生成蛋氨酸的甲基供体,并导致血浆Hcy水平升高,TT基因型个体的Hcy水平较CC或CT基因型可升高约25%。 C677T分布频率存在种族及地区差异,在非洲撒哈拉地区及加拿大北部人群T等位基因频率最低,而南欧及南美人群分布频率最高。C677T多态性是多种疾病的独立风险因子。如:阿滋海默病、心血管疾病、血栓及栓子形成、肿瘤等,与神经管闭合不全及其它先天发育缺陷及妊娠综合症相关,还可能影响某些药物代谢,可能由于合成S-腺苷蛋氨酸所需的5—甲基四氢叶酸的不足,TT基因型者外周淋巴细胞DNA甲基化水平低于CC基因型个体,因而与肿瘤发生相关。
[Abstract]:Homocysteine homocysteine homocysteine (homocysteine) is an amino acid produced during the metabolism of transmethylated and transthiocarbamate. The increase of plasma Hcy increases the risk of many diseases, including vascular diseases. Coronary heart disease, thrombosis, stroke, neural tube dysplasia and diabetic nephropathy. Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of Hcy. Irreversible reaction of 10-methylenetetrahydrofolic acid reduction to 5-methyltetrahydrofolic acid. MTHFR gene is the most common polymorphism of 677 nucleotides. 鈫扵 replacement of C677TN, the alanine of the active region of the enzyme was replaced by valine valine (Vala) to produce thermostable enzyme, which obstructed the synthesis of 5-methyltetrahydrofolic acid (5-methyltetrahydrofolic acid). The latter was a methyl donor to produce methionine from Hcy and increased the level of plasma Hcy. The Hcy level of individuals with TT genotype was about 25% higher than that of CC or CT genotypes. There were ethnic and regional differences in the distribution of C677T, and the frequency of T allele was the lowest in sub-Saharan Africa and northern Canada. In southern Europe and South America, the highest frequency of .C677T polymorphism is an independent risk factor for many diseases, such as Alzheimer's disease, cardiovascular disease, thrombosis and embolus formation, tumor and so on. Associated with neural tube insufficiency and other congenital developmental defects and pregnancy syndrome, it may also affect the metabolism of certain drugs, possibly due to a lack of 5-methyl-tetrahydrofolic acid necessary for the synthesis of S-adenosylmethionine. The DNA methylation level of peripheral lymphocytes in TT genotype was lower than that in CC genotype individuals, so it was associated with tumorigenesis.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R346

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