冠心病患者血浆凝血因子Ⅶ水平及其基因多态性研究

Study on plasma coagulation factor Ⅶ(FⅦ) levels and polymorphisms of FⅦ gene in patients with coronary heart disease

目的 研究冠心病 (CHD)患者血浆凝血因子Ⅶ (FⅦ )水平及其基因多态性。方法 对 6 0例CHD患者 [其中急性心肌梗死 (AMI) 33例 ]及正常对照者 149名的血浆活化因子Ⅶ (FⅦa)、FⅦ活性(FⅦc)与FⅦ抗原 (FⅦ :Ag)进行测定。应用PCR、限制性片段长度多态性分析及琼脂糖凝胶电泳的方法鉴定FⅦ基因中的 5个可能与血栓有关的多态性位点 :- 40 1G/T、- 40 2G/A、5′F7A1/A2、IVS7H5 /H6 /H7/H8和R35 3QM1/M2。结果 与正常对照组相比 ,CHD组的FⅦa、FⅦc与FⅦAg平均值均有升高 ,但仅AMI组FⅦa与FⅦc的增高有统计学意义 (P <0 .0 5 ) ;AMI组IVS7基因型频率与正常对照组比较差异有显著性 (P <0 .0 5 ) ,其余各组间各基因型频率与等位基因频率差异均无显著性 ;- 40 2A纯合子与 - 40 2G纯合子相比 ,血浆FⅦ :Ag水平显著升高 (P <0 .0 5 )。结论 血浆FⅦa与FⅦc增高 ,可能对AMI时冠状动脉血栓形成有促进作用 ;AMI组IVS7基因型频率与正常对照组比较差异有显著性 ;而且 - 40 2A纯合子血浆FⅦ :Ag水平显著高于 - 40 2G纯合子 ,故 - 40 2G/A多态性可能主要是影响血浆FⅦ :Ag水平 。

Objective To investigate the plasma levels of coagulation factor Ⅶ(FⅦ) and polymorphisms of FⅦ gene in patients with coronary heart disease(CHD), and evaluate the effect of plasma FⅦ levels and FⅦ gene polymorphisms on CHD. Methods Plasma FⅦa, FⅦ:Ag and FⅦc were measured and polymorphisms of FⅦ gene were analyzed in 149 control cases and 60 CHD cases, including 33 acute myocardial infarction (AMI)cases by a combination of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis. Results FⅦa, FⅦc in AMI group were significantly higher than that in control group, but FⅦ:Ag wasn’t. There were no significant difference in plasma FⅦa, FⅦ:Ag and FⅦc between CHD and control group. The IVS7 genotypic frequency in AMI group was significantly different from that in control group. There was no significant difference in genotypic frequencies and allelic frequencies in other polymphism sites. FⅦ:Ag was significantly higher in -402A homozygote than that in -402G homozygote. Conclusions Increased FⅦ levels, especially FⅦa and FⅦc in plasma, may contribute to coronary artery thrombosis. There was significant difference in IVS7 genotype frequency between control and AMI groups, but the rest weren’t significantly different. FⅦ:Ag was significantly higher in -402A homozygote than that in -402G homozygote. Polymorphism of -402 G/A may play an indirect role in AMI by regulating plasma FⅦ levels.