冠心病并高同型半胱氨酸血症患者甲硫氨酸合成酶基因突变的研究

Mutation of methionine synthase gene in coronary heart disease and hyperhomocysteinemia

目的:研究中国人冠心病并高同型半胱氨酸血症患者甲硫氨酸合成酶(MS)基因突变的情况。方法:应用聚合酶链反应-单链构象多态性分析(PCR-SSCP)以及DNA测序技术,检测60例患者MS基因中与结构和功能密切相关的10个外显子的点突变情况。结果:除已知的31外显子区3个SNP位点比较常见外,还发现了1个新的点突变,3 869位为A/G杂合子(A→G的错义突变可使1 195位氨基酸由异亮氨酸变为缬氨酸),此患者的血浆同型半胱氨酸血水平明显高于正常,为30.93μmol.L-1。此外发现32内含子1个新的G/T多态性。结论:MS某种基因突变可能是影响MS酶功能及高同型半胱氨酸血症的原因之一。

Objective To investigate the mutation of methionine synthase（MS） gene in Chinese patients with coronary heart disease and hyperhomocysteinemia. Method Polymerase chain reaction-single strand conformation polymorphism（PCR-SSCP） and DNA sequencing were used to amplify and analysize 10 exons of MS gene in 60 patients. Results One novel missense mutation（A3869G,that is I1195V）in exon 31 and novel SNP（ G to T）in intron 32 were identified. In addition, three nonsense mutation described previously in exon 31 were detected. Conclusion Some mutations of methionine synthase gene probably result in MS disorder and hyperhomocysteinemia.