血浆同型半胱氨酸与早发缺血性脑卒中易感相关性

Association of Plasma Homocysteine with susceptible to Early-onset ischemic stroke

目的 探讨血浆同型半胱氨酸(homocysteine, Hcy)水平和5,10-亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase, MTHFR)基因C677T多态性与早发大动脉粥样硬化型(large artery atherosclerosis, LAA)缺血性脑卒中(ischemic stroke, IS)的易感相关性。方法 采用基于群体的病例/对照相关研究,收集病例组急性早发(年龄≤55岁)LAA IS患者847例和对照组样本1765例。应用酶联免疫吸附试验测定血浆Hcy水平。基因分型应用Sequenom Mass Array质谱技术,使用SpectroCHIP-G384芯片单链延伸法。采用二元Logistic方法计算OR值和95%CI。结果 病例组与对照组间C677T的TT纯合基因型频率分别为2.13%和0.85%,差异有统计学意义(P=0.007)。在病例组中,TT基因型携带者的LAA IS易感风险性较CC型增加2.578倍(OR=2.578,95%CI:1.291~5.150,P=0.007)。病例组较对照组血浆Hcy水平明显升高,分别为14.04±7.77μmol/L和11.04±4.51μmol/L,差异有统计学意义(P<0.001)。病例组中,TT基因型携带者的血浆Hcy水平最高;CT基因型居中,CC基因型最低,依次为22.26±11.11μmol/L、19.98±8.69μmol/L和11.78±2.19μmol/L。结论 MTHFR基因C667T多态性与早发LAA缺血性脑卒中易感相关,通过降低MTHFR酶活性,增加血浆Hcy水平参与疾病的发生。

Objective To investigate the association of plasma homocysteine(Hcy)level and 5,10-methylenetetrahydrofolate reductase(MTHFR)gene C677T polymorphisms with early-onset large artery atherosclerosis(LAA)ischemic stroke(IS).Methods A population-based case-control study was conducted,a total of 847 patients with acute early-onset(age≤55 years)LAA IS in the case group and 1765 patients in the control group were collected.Plasma Hcy level were detected by enzyme-linked immunosorbent assay(ELISA).Genotyping was performed by Sequenom Mass Array Mass spectrometry using Spectrochip-G384 chip single chain extension method.The OR and 95%CI were calculated by binary Logistic regression.Results The TT homozygous genotypes frequencies of C677T in case group and control group were 2.13%and 0.85%,respectively,and the difference was statistically significant(P=0.007).In the case group,the TT genotype carriers was 2.578 times more susceptible to IS than that in subjects with CC genotype carriers(OR=2.578,95%CI:1.291-5.150,P=0.007).The plasma Hcy level in the case group were significantly higher in case group than that in control group(14.04±7.77μmol/L vs 11.04±4.51μmol/L),and the difference was statistically significant(P<0.001).In the case group,the plasma Hcy level of TT genotype carriers were the highest,the CT genotype was in the middle,and the CC genotype was the lowest,which were 22.26±11.11μmol/L,19.98±8.69μmol/L,11.78±2.19μmol/L,respectively.Conclusion MTHFR gene C677T polymorphism is associated with susceptibility to LAAIS,and is involved in the occurrence of disease by decreasing MTHFR enzyme activity and increasing plasma Hcy level.