血清同型半胱氨酸及其代谢相关基因MTHFR多态性与缺血性脑卒中发生及预后的关系

目的 分析血清同型半胱氨酸(HCY)水平及其代谢相关基因多态性与缺血性脑卒中发生关系,并初步评估影响缺血性脑卒中预后的危险因素,为临床的诊治及预后分析提供实验室依据,以便及时进行临床干预.方法 收集187例缺血性脑卒中患者的全血及血清样本,其中短暂性脑缺血发作(TIA)组82例、脑梗死组105例(包括可逆性神经功能障碍、进展性卒中和完全性卒中),以同期188例体检健康者作为健康对照组.全自动生化仪检测血清HCY、GLU、CHO、TG,DNA测序法检测MTHFR基因rs1801133及rs1801131位点基因型及等位基因分布频率.各组间HCY、GLU、CHO及TG比较采用单因素方差分析,MTHFR基因多态性比较使用卡方检验,采用二分类Logistic回归分析对缺血性脑卒中的预后因素进行评估.结果 脑梗死组血清HCY、GLU、CHO及TG水平均显著高于TIA组和健康对照组(P＜0.001),且脑梗死组HCY显著高于TIA组(P＜0.05);脑梗死组和TIA组MTHFR基因rs1801133位点TT基因型及T等位基因频率,rs1801131位点CC基因型及C等位基因频率显著高于健康对照组(P＜0.05),而前两组间差异无统计学意义(P＞0.05),且TT和CC基因型能显著升高各组人群的血清HCY水平(P＜0.05).多因素Logistic回归分析显示血清HCY、GLU、CHO、TG以及年龄是影响缺血性脑卒中90天预后的独立危险因素.结果 血清HCY水平与缺血性脑卒中的发生发展及预后密切相关,体内HCY代谢关键酶MTHFR基因rs1801133及rs1801133位点突变可能通过影响血清HCY水平来影响缺血性脑卒中的发生发展.

The Correlation Analysis Between Serum Homocysteine,the Polymorphisms of MTHFR and the Development and Prognosis of Ischemic Stroke

Objective To analyze the relationship between serum homocysteine (HCY) level,polymophisms of methylene tetrahydrofolate reductase(MTHFR) and the development of ischemic stroke,and to investigate the prognostic value of HCY for ischemic stroke,in order to provide a basis for clinical laboratory diagnosis,treatment,prognosis and timely clinical intervention.Methods Whole blood and serum samples were collected from 187 patients with ischemic stroke,including 82 patients with transient ischemic attack(TIA),105 patients with cerebral infarction (including reversible neurological dysfunction,stroke in progression and Completeness of stroke).Automatic biochemical analyzer was detected serum Hcy (enzymatic cycling assay),glucose (hexokinase method),CHO (CHOD-PAP method) and TG (GPO-PAP method),which were compared by one-way ANOVA.The genotypes and alleles of rs1801133 and rs1801131were detected by direct sequencing,which were compared by x2 test.The ischemic stroke prognostic factors were assessed by Multivariate Logistic regression analysis.Results HCY,GLU,CHO and TG levels of cerebral infarction group and TIA group were significantly higher than that of control group(P ＜0.001),and the difference of HCY level between cerebral infarction group and TIA group was also significantly (P ＜ 0.05).Significantly higher frequencies of TT and CC genotype and T and C alleles were observed in cerebral infarction group in rs1801133 and rs1801131 respectively when compared to TIA group and control group(P ＜0.05),but no statistical differences were recorded between TIA group and control group (P ＞ 0.05).TT and CC genotype can significantly increase the serum HCY levels in all groups.Multivariate Logistic regression analysis showed that serum HCY,GLU,CHO,TG levels and age were independent risk factor for 90 days prognosis of ischemic stroke.Conclusion Point mutations in MTHFR gene(rs1801133 and rs1801131) might be related to HCY metabolism,which might be responsible for the development of ischemic stroke.