同型半胱氨酸及其酶基因多态性与脑血栓形成的关系

The relationship between homocysteine, polymorphism of its enzymes and cerebral thrombosis

目的探讨血浆同型半胱氨酸(Hcy)及其代谢酶N5,10亚甲基四氢叶酸还原酶(MTHFR)和胱硫醚β合成酶(CBS)基因多态性与脑血栓形成的关系。方法对87例脑血栓形成患者和80例对照者,应用高效液相色谱荧光法测定血浆Hcy浓度,应用聚合酶链限制性内切酶片段长度多态性分析和扩增阻滞突变体系法检测MTHFR及CBS基因型。结果病例组血浆Hcy浓度为(15.28±4.33)μmol/L,显著高于对照组的(11.32±3.86)μmol/L(P<0.001);不同基因型对血浆Hcy浓度影响不一致;两组间基因型分布、纯合子频率和等位基因频率无显著性差异(P>0.05)。结论血浆Hcy浓度升高是脑血栓形成的独立危险因素,单纯的MTHFR和CBS突变不能被确定为脑血栓形成的独立遗传危险因素。

Objective To explore the relationship between plasma homocysteine （Hcy）, polymorphism in 5. 10-methylenetetra hydrofolate reductase （MTHFR） and cystathionine-β-synthase （CBS）, and cerebral thrombosis. Methods 87 subjects with first ever acute cerebral thrombosis and 80 controls were studied. The plasma Hcy levels were measured using high-performance liquid chro matography-fluorescence detection （HPLC-FD）. The polymorphism in MTHFR was determined by a polymerase chain reaction （PCR） assay and subsequent restriction enzyme digestion and that in CBS was determined by amplification refractory mutation system （ARMS）. Results The fast plasma Hcy level in the patient group was （15. 28 ± 4. 33）μmol/L significantly higher than that （11. 32±3. 86）μmol/L. in the control group （P〈0. 001）. Different genotype had different influence on the plasma Hcy levels. There were no differences in genotype frequencies or allele frequencies between the patient group and control group （ P〈0.05）. Conclusion Common mutations in MTHFR, CBS GBS and CBS T833C lead to hyperhomocysteinemia. Hyperhomocysteinemia. but not common mutations in MTHFR and CBS is associated with the increased incidence of cerebral thrombosis.