缺血性心脑血管病患者血浆同型半胱氨酸水平及其代谢相关酶基因多态性分析

目的　了解缺血性心脑血管病患者血浆同型半胱氨酸 (Hcy)水平的变化 ,分析该变化与Hcy代谢相关酶基因变异的相关性。方法　用高效液相色谱结合荧光检测法测定 80名正常人 ,86例脑梗死 ,6 6例心肌梗死患者血浆总同型半胱氨酸 (tHcy)浓度 ,分析血浆tHcy水平与缺血性心脑血管疾病与胱硫醚 β 合成酶 (CBS)基因 844ins6 8、甲硫氨酸合成酶 (MS)基因A2 75 6G、亚甲基四氢叶酸还原酶(MTHFR)基因C6 77T三种Hcy代谢相关酶基因突变之间的相关性。结果　缺血性心脑血管病患者血浆tHcy水平 脑梗死组 (19.5 9± 10 .6 5 ) μmol/L ,心肌梗死组 (2 1.13± 9.5 7) μmol/L]较正常对照组(13.73± 4.78) μmol/L]显著升高 (P <0 .0 5 ) ;MTHFRC6 77T纯合突变者血浆tHcy水平无论在正常对照组或患者组均较野生型及杂合突变者明显升高 (P <0 .0 5 )。MSA2 75 6G ,CBS 844ins6 8基因突变者血浆tHcy水平差异无显著性。结论　高Hcy血症是缺血性心脑血管病的重要危险因子 ,MTHFRC6 77T纯合突变可能是导致血浆Hcy水平轻、中度增高的遗传决定簇。

Correlation analysis between plasma homocysteine level and polymorphism of homocysteine metabolism related enzymes in ischemic cerebrovascular or cardiovascular diseases

OBJECTIVE: To investigate the changes of plasma homocysteine (Hcy) level in patients with ischemic cerebrovascular or cardiovascular disease and analyze the relationship between plasma Hcy levels and the mutations in Hcy metabolism related enzymes, including methylene tetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthetase (CBS) 844ins68 and methionine synthetase (MS) A2756G. METHODS: By using the HPLC-FLD method, the plasma total homocysteine (tHcy) concentration was determined in 86 patients with cerebral infarction, 66 with myocardial infarction and 80 healthy controls. The association of plasma tHcy levels with cardiovascular or cerebrovascular disease and mutations of MTHFR C677T, CBS 844 ins 68 and MS A2756G were evaluated by statistic methods. RESULTS: In the patient groups, the plasma tHcy concentrations increased significantly as compared with healthy controls. The individuals homozygous for MTHFR C677T mutation had significantly higher plasma Hcy levels. CONCLUSION: Hyperhomocysteinemia is an important risk factor for ischemic cerebrovascular and cardiovascular disease. The homozygosity of MTHFR C677T may contribute to the increase of plasma Hcy and vascular damage.