亚甲基四氢叶酸还原酶基因C677T、β-纤维蛋白原基因G448A多态性与缺血性卒中遗传易感性的关系

Relationship between C677T polymorphism of methylenctetrahydro fo late reductase gene/G448A polymorphism of β-fibrinogen gene and genetic susceptibility of ischemic stroke

目的探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因C677T、β-纤维蛋白原（β—fibrinogen,β-Fg）基因G448A多态性与缺血性卒中遗传易感性的关系。方法采用寡核苷酸芯片技术对88例缺血性卒中患者及与其配对的88名对照者进行单核苷酸多态性位点检测和分析。结果缺血性卒中患者组MTHFR基因T纯合基因型、杂合基因型和T等位基因频率分别为17．0％、50．0％和42．05％，对照组为11．4％、36．4％和29．55％，两组间MTHFR基因C677T基因型频率（P=0．034）和等位基因频率（P=0．014）分布有显著差异，β—Fg基因杂合基因型和A等位基因频率分别为27．3％和15．91％，对照组为25．0％和14．77％。多元logistic回归分析显示，MTHFR基因C677TCT基因型与缺血性卒中发病有关（优势比为2．181，95％CI1．138～4．181；P〈0．05）；β—Vg基因G448A与缺血性卒中无显著相关性，其与MTHFR基因C677T位点无协同作用。结论MTHFR基因C677T位点突变可能是缺血性卒中发病的遗传因素之一。

Objective To investigate the relationship between the C677T polymorphism of the methylenetetrahydrofolate reductase （MTHFR） gene/G448A polymorphism of the β-fibrinogen （β-Fg） gene and genetic susceptibility of ischemic stroke. Methods Single nucleotide polymorphism loci in 88 patients with ischemic stroke and 88 matched controls were detected and analyzed by oligonucleotide microarray technology. Results The frequencies of MTHFR T homogenetic type, heterogenetic type, and the T allele were 17.0%, 50.0%, and 42.05% respectively in the ischemic stroke group, and they were 11.4%, 36.4%, and 29.55 % respectively in the control group. There were significantly differences in the distributions of the MIHFR C677T genotype frequencies and allele frequencies between the 2 groups （P =0. 034 and P =0. 014）. The frequencies of β-Fg gene heterozygons genotype and A allele were 27.3% and 15.91%, respectively in the ischemic stroke group, and they were 25.0% and 14.77% in the control group. Multiple logistic regression analysis showed that MTHFR gene C677T locus CT genotype was associated with the onset of ischemic stroke （odds ratio OR 2. 181,95% CI, 1. 138-4. 181 ; P 〈0.05）. There was no significant correlation between the G448A polymorphism of the β-Fg gene and ischemic stroke, and they did not have synergy with MTHFR gene C677T. Conclusiosn The C677T mutation of the MTHFR gene may be one of the genetic factors of the onset of ischemic stroke.