Varela M L, Adamczuk Y P, Forastiero R R, Martinuzzo M E, Cerrato G S, Pombo G, Carreras L O
Department of Haematology, Thrombosis and Haemostasis, Favaloro University, Buenos Aires, Argentina.
Thromb Res. 2001 Dec 1;104(5):317-24. doi: 10.1016/s0049-3848(01)00384-x.
Factor V Leiden (FVL) and the prothrombin 20210A (PT-20210A) variant are well-known risk factors for venous thromboembolism (VT). The thermolabile variant (TT) of the methylenetetrahydrofolate reductase (MTHFR) gene, and homozygosity for the 4G allele of the promoter region of the plasminogen activator inhibitor-1 (PAI-1) are potential genetic polymorphisms that have not been consistently associated with increased risk of VT. A case-control study was performed on 192 consecutive unrelated patients referred for evaluation of thrombophilia because of VT and 200 healthy controls. FVL was found in 10.4% of patients compared to 3.0% of controls, while 6.3% of patients were carriers of the PT-20210A allele compared to 2.0% of controls. The adjusted odds ratios (OR) were 5.92 and 4.03 for FVL (P=.001) and the PT-20210A (P=.033), respectively. The prevalence of homozygotes for MTHFR (TT) and PAI-1 (4G/4G) among patients and controls were 13.7% versus 13.0% and 21.6% versus 23.5%, respectively (P=ns). A total of 121 patients underwent a complete screening for FVL, the PT-20210A, protein C (PC), protein S (PS), antithrombin III (ATIII), levels of factor VIII, and antiphospholipid antibodies (aPL). In 59 patients (48.8%) at least one defect was found, being a single defect in 55 and combined defects in 4 patients. Plasma levels of homocysteine (Hcy) were measured in 138 patients and 144 controls. Subjects from both groups carrying the MTHFR-TT variant had higher Hcy levels than those with the normal genotype. Hyperhomocysteinemia (HHcy) by itself is a risk factor for VT (OR 4.92, P<.0001). We conclude that FVL and the PT-20210A are risk factors for VT as well as Hcy levels, but the MTHFR and PAI-1 polymorphisms do not appear to be associated with VT in our country.
凝血因子V莱顿突变（FVL）和凝血酶原20210A（PT - 20210A）变异是静脉血栓栓塞症（VT）众所周知的危险因素。亚甲基四氢叶酸还原酶（MTHFR）基因的不耐热变异体（TT）以及纤溶酶原激活物抑制剂-1（PAI - 1）启动子区域4G等位基因的纯合性是潜在的基因多态性，它们与VT风险增加之间的关联并不一致。对192例因VT前来评估血栓形成倾向的连续非亲属患者和200例健康对照进行了一项病例对照研究。在患者中发现FVL的比例为10.4%，而对照组为3.0%；患者中PT - 20210A等位基因携带者的比例为6.3%，而对照组为2.0%。FVL和PT - 20210A的校正比值比（OR）分别为5.92（P = 0.001）和4.03（P = 0.033）。患者和对照组中MTHFR（TT）和PAI - 1（4G/4G）纯合子的患病率分别为13.7%对13.0%以及21.6%对23.5%（P = 无统计学意义）。共有121例患者接受了FVL、PT - 20210A、蛋白C（PC）、蛋白S（PS）、抗凝血酶III（ATIII）、因子VIII水平以及抗磷脂抗体（aPL）的全面筛查。在59例患者（48.8%）中发现至少一种缺陷，其中55例为单一缺陷，4例为复合缺陷。对138例患者和144例对照测量了血浆同型半胱氨酸（Hcy）水平。两组中携带MTHFR - TT变异体的受试者的Hcy水平均高于基因型正常者。高同型半胱氨酸血症（HHcy）本身就是VT的一个危险因素（OR 4.92，P < 0.0001）。我们得出结论，FVL和PT - 20210A以及Hcy水平是VT的危险因素，但在我国，MTHFR和PAI - 1多态性似乎与VT无关。
