血浆同型半胱氨酸水平及其代谢酶基因多态性与脑梗死的相关性研究

目的 通过探讨同型半胱氨酸(homocysteinemia,Hcy)及其主要代谢酶突变基因与脑梗死的关系,明确遗传因素与脑梗死发病的关联性,为指导临床提供理论依据.方法 选择脑梗死患者与正常健康者各60例分别为脑梗死组、正常对照组.采用高效液相色谱法(high-performance liquid chromatography,HPLC)测定血浆Hcy水平,并应用聚合酶链式反应-限制性片段长度多态分析技术(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)测定基因表型.结果 正常对照组与脑梗死组比较,Hcy水平明显偏高(P＜0.01),患者组有无高血压病史、高血脂病史、糖尿病病史,Hcy水平差异无统计学意义(P＞0.01).脑梗死组亚甲基四氢叶酸还原酶(methylenetetralydrofolate,MTHFR)基因TT基因型与正常组比较差异有统计学意义(P＜0.01),T等位基因频率明显高于正常对照组(P＜0.01).MTHFR C677T基因型和等位基因频率分布与正常组比较差异均有统计学意义(P＜0.01).MTHFR基因C677T纯合子基因型Hcy水平显著高于野生型(P＜0.01).丝氨酸在胱硫醚β合成酶(cystathionineβ-synthase,CBS)基因T27796C纯合子基因型血浆Hcy水平与杂合子基因型比较差异有统计学意义(P＜0.01),显著高于野生型(P＜0.01).Logistic回归分析脑梗死血浆Hcy水平和MTHFR C677T纯合子基因型关系密切.结论 Hcy水平与脑梗死的发病有一定关联性,可能是该病发生的一个独立危险因素.MTHFR基因C677T位点纯合子突变、CBS基因T27796C位点纯合子突变均可致血浆Hcy水平增高,可能是脑梗死发生的遗传因素.

Correlation of Plasma Homocysteine Levels and Metabolic Enzyme Gene Polymorphisms with Cerebral Infarction

Objective To explore the relationship between the Hcy and its main metabolic enzymes and cerebral infarction,to clarify the association between genetic factors and cerebral infarction in order to provide theoretical basis for clinical guidance.Methods We enrolled 60 patients with cerebral infarction and normal patients as cerebral infarction group and normal control group.Plasma Hcy levels were determined by HPLC,and the gene phenotype was determined by PCR-RFLP.Results Hcy level was significantly higher (P ＜0.01).There were no significant differences when compared history of hypertension,hyperlipidemia and diabetes mellitus(P ＞ 0.01) between two groups.MTHFR genotype of TT gene in the cerebral infarction group was significantly different(P ＜ 0.01) when compared with the control group.The frequency of T allele was significantly higher than that of the control group(P ＜0.01).There were significant differences in the frequency distribution of C677T MTHFR genotype and allele (P ＜ 0.01).The level of C677T homozygous genotype MTHFR in Hcy gene was significantly higher than that in wild type(P ＜ 0.01).There was a significant difference on plasma Hcy levels between CBS gene T27796C homozygous genotype and heterozygous genotype (P ＜ 0.01),which was significantly higher than that of wild type (P ＜ 0.01).Logistic regression analysis showed a close relationship between plasma Hcy levels and C677T MTHFR homozygous genotype in patients with cerebral infarction.Conclusion The level of Hcy is related to the incidence of cerebral infarction,which may be an independent risk factor for the occurrence of cerebral infarction.Homozygous mutations of MTHFR C677T locus and T27796C mutation in CBS gene may lead to increased plasma CY H level,which may be a genetic factor in the occurrence of cerebral infarction.