同型半胱氨酸及代谢酶基因多态性与脑卒中的相关性研究  

The relationship of plasma homocysteine levels and polymorphism in homocysteine metabolism related enzymes with brain stroke

作　　者：傅毅[1] 刘建荣[1] 倪培华[2] 应雅韵[2] 陈生弟[1] 

机构地区：[1]上海第二医科大学附属瑞金医院神经内科,200025 [2]上海第二医科大学附属瑞金医院临床检验系,200025

出　　处：《中华老年医学杂志》2005年第6期413-417,共5页Chinese Journal of Geriatrics

基　　金："脑卒中二级预防和早期干预的多中心;前瞻性研究"上海市科委重大项目(03DZ19702)

摘　　要：目的进一步确定亚甲基四氢叶酸还原酶(MTHFR)基因C677T、胱硫醚β合成酶(CBS)基因844ins68、T27796C和甲硫氨酸合成酶(MS)基因A2756G这4种基因突变在脑卒中发病中的意义。方法选择年龄及性别基本匹配的脑梗死组78例、脑出血组26例、神经系统其他疾病组29例和健康老年组50例,采用酶联免疫分析法测定受检者血浆同型半胱氨酸(Hcy)浓度,并运用多聚酶链反应限制性内切酶片段长度多态性技术,检测基因表型。结果脑梗死组和脑出血组血Hcy浓度明显高于神经系统其他疾病组和健康老年组。CBS844ins68及MSA2756G突变频率较国外报道明显低。此外,C677T纯合突变型的Hcy水平均高于野生型和杂合突变型,CBST27796C基因杂合子突变则可能使Hcy水平降低;而4种基因各组之间基因型频率差异无统计学意义。结论Hcy水平与脑卒中的发生有一定联系。CBS844ins68和MSA2756G突变可能存在种族或地域差异,MTHFRC677T纯合子突变可能是导致血浆总Hcy(tHcy)水平升高的遗传决定簇,而CBST27796C基因杂合子突变可能引起tHcy水平的降低;4种基因突变符合遗传平衡定律。Objective To explore the significance of gene mutations of methylenetetrahydrofolate reductase(MTHFR) C677T,cystathionine β-synthase(CBS)844ins68,T27796C and methionine synthase (MS A2756G) in the development of brain stroke. Methods There were no obvious differences in age and sex among the four groups. The plasma homocysteine (Hcy) levels of 78 patients with cerebral infarction, 26 patients with cerebral hemorrhage, 29 patients with other neurological diseases and 50 healthy control elders were measured by enzyme-linked immunoassay. Moreover,the genotypes of MTHFRC677T, CBS844ins68, CBST27796C and MSA2756G were detected by PCR-RFLP in four groups. Results The mean plasma Hcy levels in cerebral infarction or in cerebral hemorrhage was significantly higher than those in other neurological diseases or in healthy control elders. The prevalences of CBS 844ins68 and MS A2756G in the cohort studies were obviously lower than those in Caucasian populations. The plasma Hcy level in C677T homozygote mutation was higher than that in wild type or heterozygote. However,heterozygote mutation of CBS T27796C gene reduced Hcy concentration. There were no significant differences in the frequencies of MTHFR,CBS and MS mutations among four groups. Conclusions Hcy might be associated with brain stroke. Moreover,the prevalences of gene mutations of CBS 844ins68 and MS A2756G might vary with different ethnic groups or geographic regions. The homozygosity of MTHFR C677T might contribute to the increase of total plasma Hcy, and CBS T27796C gene heterozygote mutation might lower the raised total Hcy. In addition, four gene mutations are consistent with the law of heredity balance.

关 键 词：代谢酶基因多态性 脑卒中 相关性研究 限制性内切酶片段长度多态性技术 亚甲基四氢叶酸还原酶 844ins68 胱硫醚Β-合成酶 血浆同型半胱氨酸 基因C677T 甲硫氨酸合成酶 酶联免疫分析法 多聚酶链反应 基因突变 其他疾病 神经系统 

分 类 号：R743.3[医药卫生—神经病学与精神病学]