叶酸、维生素B_(12),MTHFR基因及血浆同型半胱氨酸水平与Alzheimer病关系的研究(英文)

Relationship between folate, vitamin B_(12), plasma homocysteine levels and polymorphisms of MTHFR gene in Alzheimer′s disease*

目的探讨叶酸、维生素B12、N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因及血浆同型半胱氢酸(Hcy)水平与Alzheimer病(AD)的关系。方法运用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测42例AD及40例正常老年人MTHFR基因多态性,用高效液相色谱仪和电化学检测法检定42例AD及40例正常老年人血浆总Hcy水平,同时测定血浆叶酸及维生素B12水平。结果MTHFR基因型有3种,即纯合子(T/T)型,杂合子(T/C)型,纯合子(C/C)型。患者组基因型和等位基因频率与正常对照组相比,差异均无显著性(P>0.05)。AD组血浆总Hcy水平显著高于正常组(t=16.64, P<0.001)。AD组血浆叶酸及维生素B12水平明显低于对照组(t=7.24, 9.11, P<0.001)。结论MTHFR基因突变与AD发生无关;高同型半胱氢酸血症是AD发病的一个新的危险因素。

Objective: To study the relationship between plasma folate, vitamin B12, plasma homocysteine(Hcy) levels and the polymorphisms of MTHFR gene in Alzheimer′s disease (AD). Methods: 42 AD patients and 40 normal aged subjects were recruited in the study. The polymorphisms of MTHFR gene were analyzed using PCR-RFLP and their plasma total Hcy levels were measured using high-performance liquid chromatography with electrochemical detection. Plasma folate and serum vitamin B12 were determined for all of them. Results: There were three kinds of genotype: T/T (homozygous mutation), T/C (heterozygous mutation) and C/C (wild-type). There was no significance between the frequencies of the genotypes and alleles of MTHFR gene in AD patients and in normal elderly subjects (P >0.05). Mean total plasma homocysteine concentrations were significantly higher in AD patients than in the normal elderly subjects (t =16.64, P <0.001). Plasma folate and serum vitamin B12 concentrations were significantly lower in AD group than in control group (t =7.24, 9.11, respectively, P <0.001). Conclusions: MTHFR mutation is not associated with AD. Hyperhomocysteinemia may be a new risk factor for AD.