同型半胱氨酸和MTHFR基因多态性与缺血性脑血管病的关系

Hyperhomocysteine, methylenetetrahydrofolate reductase gene, and other risk factors in ischemic stroke

目的 探讨同型半胱氨酸 (Hcy)和 5 ,10 亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与脑血管病的关系及其影响因素。方法 比较 4 9例缺血性脑血管病患者和 5 6健康人血浆Hcy水平和MTHFR基因多态性。分析年龄、肝肾功能、吸烟、嗜酒、血浆维生素B12 、叶酸水平的影响 ,及其与脑血管病和血管狭窄的关系。结果 病例组与对照组血浆Hcy分别为 17 0 μmol/L± 9 0 μmol/L和 12 6μmol/L± 5 2 μmol/L ,两者差异有非常显著差异 (P <0 0 1)。病例组与对照组之间MTHFR基因 6 77位点T等位基因率及T/T纯合子率分别为 5 2 0 %和 4 4 0 % ,P >0 0 5 ;2 6 5 %和 2 0 0 % ,差异无显著意义 (P >0 0 5 )。另外 ,各组组内T/T纯合子与非T/T纯合子的Hcy差异有显著意义。颅内外血管狭窄与血浆Hcy水平未发现统计学有相关性。血浆叶酸和维生素B12 水平与Hcy和脑血管病均无显著关系。血尿素氮增高和吸烟者与Hcy增高有显著关系 (P <0 0 5 )。结论 本组人群MTHFR基因C6 77T突变的纯合子引起血浆Hcy水平显著增高。血浆Hcy水平和缺血性脑血管病密切相关。肾功能、吸烟等因素也与Hcy增高有关。

Objective To investigate the relation between plasma homocysteine (Hcy) and cerebral ischemic diseases and that between polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and cerebral ischemic diseases. Methods The plasma homocysteine (Hcy) and genetic polymorphism of MTHFR among forty nine cases with ischemic cerebral diseases, including 25 with acute cerebral infarction (CI) and 25 with transient ischemic attacks (TIA), were investigated. Fifty five age and sex matched healthy persons were used as controls. All the subjects underwent brain CT, carotid duplex, transcranial Doppler examination, plasma Vitamin B 12 and folic acid examination, besides examination of plasma Hcy and nucleotide 677 MTHFR genotypes. The effects of age, liver function, renal fuction, smoking, drinking, plasma vitamin B 12 , and folic acid were analyzed. Results The mean plasma Hcy was significantly higher in the CI group and TIA group (17 4±7 6 μmol/L and 16 6±5 2 μmol/L) compared with that in the control group(12 6±5 2 μmol/L, P <0 01) The odds ratio was 3 26 (95% CI, 1 05～10 09, P <0 01) The Hcy concentration was significantly higher in persons with T/T genotype than in those with C/C or CT There was no significant difference of frequency of mutant alleles (T) in site 677 of MTHFR gene and in frequency of homozygote T/T among the patients and controls (52 0% vs 44 0%, P <0 05 and 26% vs 20 0%, P >0 05). The difference of Hcy was significant between those being T/T homozygotic and those not being T/T homozygotic in defferent groups. There was no statistical correlation between plasma Hcy level and extra and intracranial stenosis of cerebral artery. Increase of BUN and smoking were significantly correlated with increase of Hcy ( P <0 05). The concentrations of plasma Vitamin B 12 and folic acid were significantly correlated with that of Hcy. Conclusion Homozygote of mutant MTHFR gene C677T causes hyperhomocystinemia. There is a significantly association between hyperhomocystinemia and ischemic cerebrovascular disease. The frequency of mutation in MTHFR genotype is higher in Chinese than in Caucasians. In addition to gene mutation, renal function and smoking are related to increase of plasma Hcy. No correlation between genotype of MTHFR and stroke is found.