胱硫醚-β-合酶(CBS)基因与冠心病发病机制的研究

Relationship between Cystathionine-β-synthase Gene and Pathogenesis of Coronary Heart Disease

目的 :研究冠心病患者血浆同型半胱氨酸(HCY)水平及HCY代谢相关酶胱硫醚 - β-合酶(CBS)基因T833C位点、G919A位点碱基突变与冠心病的关系。方法 :用酶联免疫试剂盒测定血浆HCY水平 ,采用扩增阻滞突变体系法检测CBS基因中T833C和G919A基因型。结果 :冠心病组HCY水平显著高于对照组(P<0.01)。CBS基因T833C冠心病组CC、CT、TT型频率分布及C、T等位基因频率分布 ,G919A冠心病组AA、AG、GG型频率分布及A、G等位基因频率分布 ,均与对照组有非常显著性差异(P<0.05或P<0.01)。T833C、G919A冠心病组中3种基因型的HCY水平有显著性差异(P<0.05)。冠心病组的CC、CT基因型HCY水平显著高于TT型 ,AA、AG基因型HCY水平显著高于GG型。结论 :(1)高HCY血症是冠心病发病的危险因素 ,CBS基因T833C的CC、CT突变和G919A的AA、AG突变是高HCY血症的原因。(2)CBS基因T833C。

Objective:To study the relationship between cystathionine-β-synthase(CBS)gene and pathoˉgenesis of coronary heart disease(CHD).Methods:Plasma homocystein(HCY)was determined by enzyme linked immunosorbent assay(ELISA)and the mutation of T833C,G919A transition was identified with amˉplification refractory mutation system(ARMS)methods.Results:The mean level of plasma HCY in CHD group was higher than that in control group(P<0.01).In the mutation of T833C and G919A,there were significant differences in the frequences of genotypes and allels of the two groups(P<0.05or P<0.01).There were obˉvious differences in HCY levels among the three genotypes of CBS gene T833C and G919A in CHD group(P<0.05).The plasma HCY levels in CHD group of CC and CT genotypes were much higher than those in TT.Plasma HCY concentrations in CHD patients with homozygosity(AA)and heterozygosity(AG)of G919A mutation were markedly higher than those patients without mutations(GG).Conclusion:(1)Hyperhomocysˉteinemia is an independent risk factor of CHD.CBS is the main enzyme related to homocysteine metabolism.Their genetic mutations are possibly important mechanism of hyperhomocysteinemia.(2)The CBS mutation is related with CHD.