Spiridonova M G, Stepanov V A, Puzyrev V P, Karpov R S
Institute of Medical Genetics, Tomsk Research Center, Russian Academy of Medical Sciences, Tomsk, 634050 Russia.
Genetika. 2002 Mar;38(3):383-92.
The following seven polymorphic marker loci of genes responsible for predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus responsible for angiotensin-converting enzyme insertion/deletion polymorphism for the presence or absence of the Alu insertion in the gene; the F13, PLAT, and APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci responsible for point mutations in methylenetetrahydrofolate reductase and those in angiotensinogen, respectively, and the NOS3 locus controlling the number of tandem repeats in the nitric oxide synthase gene. These loci are located on different chromosomes and encode products involved into various metabolic pathways leading to CAS. In the populations studied, significant differences between healthy subjects and patients predisposed to cardiovascular diseases were revealed with regard to the above seven markers. The 174M allele (T174M polymorphism in the ACE gene) was significantly associated with coronary atherosclerosis. It was found that specific gene combinations are involved in the CAS development and determine variation in the pathogenetically important quantitative traits.
对以下七个与冠状动脉粥样硬化(CAS)易感性相关的基因多态性标记位点进行了研究:负责血管紧张素转换酶插入/缺失多态性的ACE位点,即基因中是否存在Alu插入;分别控制凝血因子13、组织纤溶酶原激活因子和载脂蛋白A的F13、PLAT和APOA1位点;分别负责亚甲基四氢叶酸还原酶和血管紧张素原点突变的MTHFR和AGT多态性位点,以及控制一氧化氮合酶基因串联重复数目的NOS3位点。这些位点位于不同染色体上,编码参与导致CAS的各种代谢途径的产物。在所研究的人群中,就上述七个标记而言,健康受试者与易患心血管疾病的患者之间存在显著差异。174M等位基因(ACE基因中的T174M多态性)与冠状动脉粥样硬化显著相关。研究发现,特定的基因组合参与了CAS的发生发展,并决定了在发病机制上重要的数量性状的变异。