论文部分内容阅读
背景:血浆同型半胱氨酸浓度升高是动脉粥样硬化性血栓性脑梗死的独立危险因素,同型半胱氨酸在转硫化和再甲基化过程中的代谢酶N5,N10-亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因突变可致血浆同型半胱氨酸浓度升高。目的:探讨同型半胱氨酸血症、同型半胱氨酸代谢关键酶MTHFR基因突变与青年缺血性脑血管疾病的关系。设计:病例-对照观察。单位:吉林大学中日联谊医院神经内科。对象:于2003-04/2004-12吉林大学中日联谊医院神经内科收治发病2d内住院的青年脑梗死患者100例,为病例组,男73例,女27例;年龄27～45岁,平均(42±5)岁。对照组100例为同期健康体检者,男70例,女30例;年龄18～45岁,平均(39±4)岁。方法:以高效液相色谱法测定受试者空腹血浆同型半胱氨酸,采用聚合酶链反应-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MTHFR基因C677T位点和A1298C位点进行检测。主要观察指标:MTHFRC677T和A1298C基因检测,血浆同型半胱氨酸浓度与MTHFR基因型的关系。结果:纳入患者100例和正常对照100例,均进入结果分析。①MTHFRC677T和A1298C基因检测:MTHFRC677T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显著(P<0.01)。而MTHFRA1298C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无显著性(P>0.05)。②血浆同型半胱氨酸浓度与MTHFR基因型的关系:MTHFRC677T和A1298C各基因型间血浆同型半胱氨酸浓度差异有显著性(P<0.001)。2个位点突变结果LSD-t检验显示纯合子与杂合子,纯合子与野生型血浆同型半胱氨酸浓度均数差有统计学意义(P<0.05)。MTHFRC677T和A1298C杂合子与野生型血浆同型半胱氨酸浓度均数差无统计学意义(P>0.05)。结论:MTHFRC677T和A1298C突变均导致血浆同型半胱氨酸浓度明显增高。MTHFRC677T多态性位点是青年缺血性脑血管疾病的独立危险因子。MTHFRA1298C基因突变与青年缺血性脑血管疾病发病无相关性。
BACKGROUND: Elevated plasma homocysteine concentration is an independent risk factor for atherothrombotic cerebral infarction. Metabolic enzymes N5 and N10-methylene homocysteine during transsulfuration and remethylation Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene lead to an increase in plasma homocysteine concentration. Objective: To investigate the relationship between homocysteinemia and mutation of MTHFR, a key homocysteine metabolic enzyme, in young patients with ischemic cerebrovascular disease. Design: Case-control observation. Unit: Sino-Japanese Friendship Hospital, Jilin University, Department of Neurology. PARTICIPANTS: A total of 100 young patients with cerebral infarction hospitalized within 2 days of onset were enrolled in Department of Neurology, Sino-Japanese Friendship Hospital, Jilin University from April 2003 to December 2004. The patients were 73 males and 27 females, aged 27-45 years (42 ± 5) years old. The control group of 100 cases for the same period health examination, 70 males and 30 females; aged 18 to 45 years, mean (39 ± 4) years. Methods: The fasting plasma homocysteine was determined by high performance liquid chromatography (HPLC). Polymerase chain reaction - restriction fragment length polymorphism (PCR) and amplification - blocking mutagenesis were used to detect the expression of MTHFR C677T Site and A1298C site for testing. MAIN OUTCOME MEASURES: MTHFRC677T and A1298C gene detection, plasma homocysteine concentration and MTHFR genotypes. Results: 100 patients and 100 normal controls were included in the results analysis. ①MTHFRC677T and A1298C gene detection: genotype distribution, homozygote frequency and allele frequency of MTHFRC677T gene test cases and controls were significantly different (P <0.01). However, there were no significant differences in genotype distribution, homozygote frequency and allele frequency between MTHFRA1298C gene test group and control group (P> 0.05). ② The relationship between plasma homocysteine concentration and MTHFR genotypes: There was significant difference in plasma homocysteine concentrations between MTHFRC677T and A1298C genotypes (P <0.001). LSD-t test showed that there was a statistically significant difference in homozygote and heterozygous homozygotes between homozygous and wild-type plasma homocysteine concentration (P <0.05). There was no significant difference in mean homocysteine concentrations between MTHFRC677T and A1298C heterozygous and wild-type plasma (P> 0.05). Conclusion: Mutations of MTHFRC677T and A1298C lead to the significant increase of plasma homocysteine concentration. The MTHFRC677T polymorphic site is an independent risk factor for ischemic cerebrovascular disease in young people. MTHFRA1298C gene mutation and the incidence of ischemic cerebrovascular disease was not related.