Cattaneo M, Chantarangkul V, Taioli E, Santos J H, Tagliabue L
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, University of Milano, Italy.
Thromb Res. 1999 Jan 1;93(1):1-8. doi: 10.1016/s0049-3848(98)00136-4.
A common G to A transition at nucleotide 20210 of the prothrombin gene is associated with an increased risk for deep-vein thrombosis (DVT) and high plasma levels of prothrombin. We calculated the prevalences of prothrombin G20210A, factor V G1691A (also associated with high risk for DVT) and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T (associated with increased susceptibility to develop hyperhomocysteinemia) in 118 patients with a first episode of DVT and in 416 healthy controls. 15.9% of the patients and 2.3% of the controls had prothrombin G20210A (odds ratio [OR]: 8.7, 95% C.I.: 3.8-21.4); 21.1% of the patients and 3.2% of the controls had factor V G1691A (OR 7.8, 3.9-17.1); 20.5% of the patients and 21% of the controls had homozygous MTHFR C677T (OR: 1.0, 0.7-1.2). Exclusion of patients with other hereditary risk factors for DVT did not substantially modify the results. Mutant factor V and prothrombin coexisted in three patients but in no control. The concomitant presence of the MTHFR mutation did not increase the thrombotic risk associated with prothrombin G20210A. 63.2% of individuals with prothrombin G20210A had plasma levels of prothrombin in the upper quartile of distribution. After adjustment for age and sex, subjects with prothrombin levels in the upper quartile carried a slightly higher risk for thrombosis than those with lower prothrombin concentrations (OR: 1.9, 1.1-3.2). In conclusion, we found that prothrombin G20210A is relatively common in Italy and is associated with high prothrombin levels and an 8.7-fold increase in the risk for DVT. Such risk is independent of the coexistence of other known inherited risk factors for thrombosis and increases in patients with associated mutant factor V. Whether it is due to the associated increase in plasma prothrombin levels remains to be established.
凝血酶原基因第20210位核苷酸处常见的G到A转换与深静脉血栓形成（DVT）风险增加及血浆凝血酶原水平升高有关。我们计算了118例首发DVT患者和416例健康对照者中凝血酶原G20210A、因子V G1691A（也与DVT高风险相关）以及纯合亚甲基四氢叶酸还原酶（MTHFR）C677T（与发生高同型半胱氨酸血症的易感性增加相关）的患病率。15.9%的患者和2.3%的对照者存在凝血酶原G20210A（优势比[OR]：8.7，95%置信区间：3.8 - 21.4）；21.1%的患者和3.2%的对照者存在因子V G1691A（OR 7.8，3.9 - 17.1）；20.5%的患者和21%的对照者存在纯合MTHFR C677T（OR：1.0，0.7 - 1.2）。排除具有其他DVT遗传危险因素的患者后，结果无实质性改变。三名患者同时存在突变型因子V和凝血酶原，但对照者中无此情况。MTHFR突变的同时存在并未增加与凝血酶原G20210A相关的血栓形成风险。63.2%的凝血酶原G20210A个体血浆凝血酶原水平处于分布的上四分位数。在对年龄和性别进行校正后，凝血酶原水平处于上四分位数的受试者发生血栓形成的风险略高于凝血酶原浓度较低者（OR：1.9，1.1 - 3.2）。总之，我们发现凝血酶原G20210A在意大利相对常见，与凝血酶原水平升高及DVT风险增加8.7倍相关。这种风险独立于其他已知的血栓形成遗传危险因素的共存，并且在伴有突变型因子V的患者中增加。其是否归因于血浆凝血酶原水平的相关升高仍有待确定。
