血中同型半胱氨酸和亚甲基四氢叶酸还原酶C677T基因多态性与脑血管狭窄的关系

Relationship between homocysteine and methylenetetrahydrofolate reductase C677T gene polymorphisms and cerebral vascular stenosis

目的探讨血中同型半胱氨酸(HCY)水平及其代谢酶———亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与脑血管狭窄的关系。方法采用回顾性病例对照研究的方法,纳入脑血管狭窄患者85例,其中单纯颅内动脉狭窄40例,单纯颅外动脉狭窄45例。选择同期年龄和性别匹配的无脑血管狭窄者65例作为对照组。采用荧光偏振免疫法和聚合酶链反应-限制片段长度多态性技术,测定和分析各组血浆HCY水平和MTHFR C677T基因多态性。结果①脑血管狭窄组患者血浆HCY水平中位数[11.00(8.05～15.00)μmol/L]高于对照组[8.40(5.50～10.95)μmol/L],差异有统计学意义(P<0.05)。与对照组相比,颅内动脉狭窄组[11.75(8.10～15.25)μmol/L]和颅外动脉狭窄组[9.00(8.00～14.05)μmol/L]HCY水平均升高(P<0.05)。②在脑血管狭窄组和对照组中,MTHFR C677T基因突变TT纯合子的HCY水平中位数分别为[16.00(11.93～17.30)μmol/L]、[12.90(8.90～14.05)μmol/L],高于CC无突变纯合子者的[9.00(8.00～12.80)μmol/L]、[8.60(5.10～11.05)μmol/L],P<0.05。③多因素Logistic回归分析显示,高HCY血症(OR=2.686,95%CI:1.051～6.869,P=0.039)、高血压(OR=2.431,95%CI:1.226～4.822,P=0.011)是脑血管狭窄的独立危险因素。MTHFR C677T基因型多态性不是脑血管狭窄的独立危险因素(P=0.909)。结论高同型半胱氨酸血症可能是脑血管狭窄的危险因素。MTHFR C677基因型突变是影响HCY水平的重要因素,但与脑血管狭窄无明确关系。

Objective To investigate the relationship between homocysteine （HCY） and its me- tabolizing enzymes methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphisms and cerebral vascular stenosis. Methods A total of 85 patients with cerebral vascular stenosis were enrolled using the method of retrospective ease-control study, among them 40 patients had intraeranial artery stenosis only and 45 had extracranial artery stenosis only. Meanwhile, 65 age- and sex-matched healthy subjects at the same period without cerebral artery stenosis were used as control group. The levels of plasma HCY and MTHFR C677T gene polymorphisms in each group were measured and analyzed by fluorescence polarization immu- noassay and restriction fragment length polymorphism. Results （~）The median plasma HCY level （ 11.00 [ 8.05-15.00 ] ~mol/L） in patients of the cerebral vascular stenosis group was higher than that （8, 40 [5.50-10.95 ~ i^mol/L） in the control group. There was significant difference （ P 〈 0.05 ）. Compared to the control group, the HCY levels of the intracranial arterial stenosis group （11.75 [ 8.10-15.25 ] μmo]/L） and the extracranial stenosis group （9.00 [ 8.00 - 14.05 ] μmol/L） increased significantly （ P 〈 0.05 ）. （1）In the cerebral vascular stenosis group and the control group, the median HCY levels of T1- homozygous MTHFR C677T mutation were 16.00 （ 11.93 -17.30 ） μmol/L and 12.90 ± 8.90 -14.05 ] μmol/L respec- tively, which were higher than those in patients without CC homozygous mutation （9.00 [ 8.00 - 12.80 ] μmol/L,8.60[5. 10 - 11.05 ] μmoL/L） （ P 〈 0.05 ）. （1）Multivariate logistic regression analysis showed that the OR of cerebral vascular stenosis in patients with high level of HCY （OR =2. 686,95% CI 1. 051- 6. 869 ; P = 0. 039 ） and hypertension （ OR = 2.431,95 % CI 1. 226 -4. 822 ; P -- 0.011 ） were the independ- ent risk factors of cerebral vascular stenosis . There were no correlation between the MTHFR C677T geno- type and cerebral vascular stenosis （P =0. 909）. Conclusion Hyperhomoeysteinemia may be a risk fac- tor for cerebral vascular stenosis. MTHFR C677C mutation is an important factor for influencing HCY levels, however, it has no clear relationship with cerebral vascular stenosis.