MTHFR基因多态性与下肢DVT的相关性研究

An association study of methylenetetrahydrofolate reductase gene polymorphism with deep venous thrombosis

目的探讨N5,N10-亚甲基四氢叶酸还原酶(Methylenetetrahydrofolatereductase,MTHFR)基因多态性与我国东北地区人群下肢深静脉血栓形成(Deepvenousthrombosis,DVT)的关系。方法采用PCR-RFLP检测73例DVT患者和109名健康对照者MTHFRC677T、A1298C突变,计算患者组与对照组的基因型频率、等位基因频率以及突变与DVT的相关性。结果患者组677TT、677CT基因型频率和T等位基因频率分别为38.4%、49.3%和63%,明显高于对照组(分别为15.6%、46.8%和39%。χ2=19.393,P<0.01;χ2=20.200,P<0.01)。677TT和677CT基因型的个体比677CC基因型的个体发生DVT的相对危险分别约高7或3倍(ORTT=7.503,95%可信区间为2.931～19.207;ORTC=3.215,95%CI为1.391～7.434)。患者组与对照组MTHFR1298各基因型和等位基因分布无显著性差异(χ2=3.533,P>0.05;χ2=0.100,P>0.05),但1298CC677CC基因型的个体比1298AA、677CC基因型的个体发生DVT的相对危险约高16倍(OR=16.500,95%CI为1.353～201.290)。结论MTHFR基因C677T和A1298C突变可能为我国东北地区人群下肢DVT的危险因素。

Objective To investigate the relationship between MTHFR gene polymorphism and deep venous thrombosis.Methods Whole blood specimen from 73 patients with deep venous thrombosis and 109 healthy controls were obtained for detection of genotype.The genetic polymorphisms of MTHFR C677T and MTHFR A1298C was determined by PCR RFLP protocol.Results Increased frequencies of TT or TC genotype and T allele for MTHFR C677T in patients were found comparing to healthy controls(38.4% vs 15.6%,49.3% vs 46.8%,χ2=19.393,P<0.01;63% vs 39%,χ2=20.200,P<0.01).Subjects with the 677TT or 677TC genotype had a more than 7-fold or 3-fold increased risk of developing DVT (ORTT=7.503,95%CI,2.931-19.207;ORTC=3.215,95%CI,1.391-7.434) compared with those who had the 677CC genotype.No difference was found between the frenquencies of MTHFR A1298C genotype or allele in patients and those in controls, but subjects with the 1298CC and 677CC genotype had a more than 16-fold increased risk of developing DVT (OR=16.500,95%CI,1.353-201.290) compared with those who had the 1298AA and 677CC genotype. Conclusion The genetic polymorphisms of MTHFR C677T and A1298C may be associated with the development of DVT.