Van Hylckama Vlieg Astrid, Komanasin Nantarat, Ariëns Robert A S, Poort Swibertus R, Grant Peter J, Bertina Rogier M, Rosendaal Frits R
Department of Clinical Epidemiology and Haemostasis and Thrombosis Research Centre, Leiden University Medical Centre, Leiden, The Netherlands.
Br J Haematol. 2002 Oct;119(1):169-75. doi: 10.1046/j.1365-2141.2002.03797.x.
Varying results on the effect of factor XIII (FXIII) Val34Leu on venous thrombotic risk have been reported. The probability of a true association between this polymorphism and venous thrombotic risk would be enhanced by a laboratory phenotype associated with this polymorphism and with the thrombotic risk. The aim of this study was to assess the effect of FXIII Val34Leu, FXIII activity and subunit levels on venous thrombotic risk in a large case-control study, The Leiden Thrombophilia study (LETS). We found higher FXIII activity for 34Leu carriers (Leu/Leu: 158.0, Val/Val: 95.0). FXIII subunit levels were not associated with genotype. Higher FXIII activity was associated with a slightly decreased thrombotic risk [Odds ratio (OR): 0.8, 95% confidence intervals (CI): 0.5-1.3]. This effect was not present for elevated FXIII subunit levels. Higher FXIII activity was also associated with a higher dissociation index (percentage A2B2 complex dissociated after activation by thrombin for a fixed time interval). This index was higher for FXIII 34Leu carriers. The risk of deep venous thrombosis was slightly decreased for carriers of the 34Leu allele [OR: 0.9 (95%CI: 0.7-1.1)]. For homozygous 34Leu carriers the OR was 0.7 (95%CI: 0.4-1.3). This finding, suggesting a weak protective effect, was completely restricted to men. An overall estimate of thrombotic risk was calculated by using earlier reports on the risk of FXIII Val34Leu. The overall risk estimate for homozygous 34Leu carriers was 0.8 (95%CI: 0.6-1.0). In this study, a weak protective effect against venous thrombosis was found, of FXIII 34Leu as well as of increased FXIII activity.
关于凝血因子 XIII（FXIII）Val34Leu 对静脉血栓形成风险的影响，已有不同的研究结果报道。若存在一种与该多态性及血栓形成风险相关的实验室表型，那么这种多态性与静脉血栓形成风险之间存在真正关联的可能性就会增加。本研究的目的是在一项大型病例对照研究——莱顿血栓形成倾向研究（LETS）中，评估 FXIII Val34Leu、FXIII 活性及亚基水平对静脉血栓形成风险的影响。我们发现 34Leu 携带者的 FXIII 活性更高（Leu/Leu：158.0，Val/Val：95.0）。FXIII 亚基水平与基因型无关。较高的 FXIII 活性与血栓形成风险略有降低相关[比值比（OR）：0.8，95%置信区间（CI）：0.5 - 1.3]。FXIII 亚基水平升高则不存在这种效应。较高的 FXIII 活性还与更高的解离指数相关（在固定时间间隔内经凝血酶激活后 A2B2 复合物解离的百分比）。对于 FXIII 34Leu 携带者，该指数更高。34Leu 等位基因携带者发生深静脉血栓形成的风险略有降低[OR：0.9（95%CI：0.7 - 1.1）]。对于纯合 34Leu 携带者，OR 为 0.7（95%CI：0.4 - 1.3）。这一表明存在微弱保护作用的发现完全局限于男性。通过使用先前关于 FXIII Val34Leu 风险的报告，计算出了血栓形成风险的总体估计值。纯合 34Leu 携带者的总体风险估计值为 0.8（95%CI：0.6 - 1.0）。在本研究中，发现 FXIII 34Leu 以及 FXIII 活性增加对静脉血栓形成具有微弱的保护作用。
