胱硫醚β-合成酶基因突变与青年缺血性脑血管疾病的相关性

背景:高半胱氨酸与脑梗死发病相关,胱硫醚β-合酶是同型半胱氨酸代谢关键酶,其基因突变是不是脑梗死的潜在的遗传候选因素尚不清楚。目的:从遗传基因变异的角度观察胱硫醚β-合酶基因T833C位点、G919位点碱基突变与青年缺血性脑卒中发病之间的关系。设计:病例-对照分析。单位:吉林大学中日联谊医院神经内科。对象:病例组:100例,为2003-04/2004-12吉林大学中日联谊医院住院患者。均是发病2d内住院、年龄≤45岁的青年脑梗死患者。对照组:100例,为同期来院体检的正常青年人。方法:以高效液相色谱法测定受试者空腹及负荷后血浆同型半胱氨酸水平,采用聚合酶链-限制性内切酶片段长度多态性分析和扩增阻滞突变体系法,对所有受试者的胱硫醚β-合酶基因T833C位点,G919A位点进行检测。结果:200例均进入结果分析。①胱硫醚β-合酶基因T833C位点,G919A位点基因检测病例组和对照组基因型分布、纯合子频率和等位基因频率差异均没有统计学意义(P>0.05)。②血浆同型半胱氨酸浓度:G919A,T833C各基因型间有显著差异(P<0.001);二个位点突变结果LSD-t检验显示:纯合子与杂合子,纯合子与野生型,C杂合子与野生型间差异均有显著性意义(P<0.05)。结论:①胱硫醚β-合酶基因T833C,G919A位点突变均可导致血浆同型半胱氨酸浓度明显增高。②胱硫醚β-合酶基因G919A和T833C基因突变与青年脑血管病发病无直接相关性。

Association between cystathionine-beta-synthase gene mutation and ischemic cerebrovascular disease in youths

BACKGROUND: Homocysteine is associated with the attack of cerebral infarction, and cystathionine-beta-synthase (CBS) is a key enzyme of the metabolism of homocysteine, but it is still not clear whether its gene mutation is the potential candidate genic factor of cerebral infarction.OBJECTIVE: To observe the correlation of CBS base mutation at T833C and G919 sites with the attack of ischemic stroke in youths from the angle of genic mutation.DESIGN: A patient-control analysis.SETTING: Department of Neurology, China-Japan Friendship Hospital of Jilin University.PARTICIPANTS: Patient group (n=100): Young inpatients with cerebral infarction ≤ 45 years old in the China-Japan Friendship Hospital of Jilin University between April 2003 and December 2004, admitted within 2 days after attack. Control group (n=100): Normal young physical examinees in this hospital at the same period.METHODS: The levels of fasting and loaded homocysteine in plasma were detected with high performance liquid chromatography (HPLC), CBS genes at T833C and G919A sites with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system in all the subjects.RESULTS: All of the 200 subjects entered the analysis of results. ① Detection of CBS genes at T833C and G919A sites: The distribution of genotype, frequency of homozygote and that of allele had no significant differences between the patient group and control group (P ＞ 0.05). ② Concentration of homocysteine in plasma: There were significant differences among the genotypes at G919A and T833C sites (P ＜ 0.001). The results of LSD-t test of the mutation at the two sites showed that there were significant differences between homozygote and heterozygote, homozygote and wild type,as well as C heterozygote and wild type (P ＜ 0.05).CONCLUSION: ① The CBS gene mutations at both T833C and G919A sites can lead to the obvious increase of the concentration of homocysteine in plasma. ② The CBS gene mutations at T833C and G919A sites had no direct association with the attack of cerebrovascular disease in youths.