甲基四氢叶酸还原酶基因多态性与下肢动脉粥样硬化闭塞症

目的探讨同型半胱氨酸(Hcy)代谢相关酶甲基四氢叶酸还原酶(MTHFR)基因多态性、血浆Hcy、叶酸、维生素B12水平与动脉粥样硬化闭塞症的关系。方法血Hcy采用荧光偏振免疫分析法检测,叶酸的检测采用离子捕获免疫分析法(ICIA),维生素B12的检测采用非均相微粒子酶免疫分析法(MEIA),以聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析MTHFR C677T基因型。结果动脉粥样硬化闭塞症组MTHFR基因TT型、TC型及CC型频率分布及T、C等位基因频率与对照组差异有统计学意义。动脉粥样硬化闭塞症组Hcy水平为(22±13)μmol/L显著高于对照组(P<0.01)。叶酸平均浓度(2.8±1.7)ng/ml,维生素B12浓度平均(232±143)pg/ml,明显低于对照组(P<0.01)。动脉粥样硬化闭塞症组中3种基因型的Hcy水平差异有统计学意义,TT型Hcy明显高于CC型(P<0.05)。结论高Hcy血症是动脉粥样硬化闭塞症发病的危险因素,血浆Hcy水平的升高与叶酸、维生素B12的降低有关。MTHFR基因C677T的TT突变是高Hcy血症的原因,MTHFR C677T基因多态性与动脉粥样硬化闭塞症的发生相关。

Study on polymorphism of methylenetetrahydrofolate reductase gene in patients with arteriosclerosis obliterans

Objective To study the relationship among plasma homocystein （Hey）, folate, vitaminB12, C677T mutation of the Methylenetetrahydrofolate reductase （MTHFR） gene and arteriosclerosis obliterans （ASO）. Methods：Using fluorescent lightimmune teehnology to measure serum Hey, Using ion capture immunosorbent assay to measure folic acid（FA）, Using Heterogeneous Mieroparticle Enzyme Immunoassay （MEIA）to measure vitamin B12（VB12）. Results ： （1）The serum Hey in ASO patients was obviously higher than that in controls; The serum FA,VB12 were lower than those in controls（P〈0.05）.（2） Level of Hey significantly increased with the severity increased. （3）A negative correlation was found in ASO group between serum FA,VB12 and Hey（P〈0.05）. Results： There was no significant difference in the frequencies of genotype and levels in ASO group are （21. 58 ±12. 69）？mol/L . They are higher in ASO group than that in control group （P 〈 0.01）. The mean level of folate and vitaminB12 are lower in ASO group （2. 78 ±1.66） ng/ml , （231. 76 ±143. 78） pg/ml than lhat in control group （ P〈 0.01） . The plasma Hey levels in TT genotype of MTHFR gene was much higher than those in CC. Conclusion： Hyperhomocysteinemia is an independent risk factor of ASO. Hyperhomocysteinemia is related with folale and vitamlnB12 decreasing. MTHFR is the main enzyme related to homocysteine metabolism. Its genetic mutations are possibly important mechanism of hyperhomocysteinemia, but MTHFR mutation is not related with ASO.