凝血相关基因多态性与下肢深静脉血栓形成的相关性

Correlation between the Polymorphism of Coagulation-Related Genes and Lower Extremity Deep Venous Thrombosis

目的探讨rs1799963(凝血因子V基因Leiden)、rs6025(凝血酶原基因G20210A)、rs1042579(血栓调节蛋白基因c.1418C>T)及rs1801131(亚甲基四氢叶酸还原酶基因)4个凝血相关基因的多态性与下肢深静脉血栓形成的相关性。方法采用竞争性等位基因特异性聚合酶链反应(kompetitive allele specific polymerase chain reaction,KASP)技术检测150例下肢深静脉血栓患者及153例健康对照者上述4个基因分型,采集相关血液生物化学指标,建立二元Logistic回归筛选下肢深静脉血栓形成的独立危险因素,校正混杂因素后在不同遗传模式下分析下肢深静脉血栓与各指标及4种凝血相关基因多态性的相关性。结果D-二聚体、纤维蛋白原降解产物、同型半胱氨酸、性别、年龄这5个变量可能是下肢深静脉血栓形成的危险因素。将这些变量引入4种基因遗传模式,在二元Logistic回归环境下进行校正,结果显示,rs1042579突变在显性遗传模式下与下肢深静脉血栓形成具有相关性。结论rs1799963、rs6025、rs1801131的基因多态性与下肢深静脉血栓形成无明显相关性,rs1042579的基因多态性在显性遗传模式下发挥作用,可能是下肢深静脉血栓形成的独立危险因素。

Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes,rs1799963(coagulation factor V gene Leiden),rs6025(prothrombin gene G20210A),rs1042579(thrombomodulin protein gene c.1418C>T)and rs1801131(methylenetetrahydroflate reductase gene)and lower extremity deep venous thrombosis(LEDVT).Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction(KASP),then related blood biochemical indicators were collected,binary Logistic regres-sion was established to screen the independent risk factors of LEDVT,and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed.Results Five variables,D-dimer,fibrinogen degradation product,homocysteine,sex and age might be the risk factors of LEDVT.These variables were put into 4 genetic inheritance models,and adjusted in binary Logistic regression.The results sug-gested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode.Conclusion The gene polymorphism of rs1799963,rs6025 and rs1801131 has no significant correlation with the formation of LEDVT.The gene polymorphism of rs1042579 plays a role under dominant in-heritance mode,and might be an independent risk factor for formation of LEDVT.