Corral Javier, Antón Ana I, Quiroga Teresa, González-Conejero Rocio, Pereira Jaime, Roldán Vanessa, Vicente Vicente, Mezzano Diego
Servicio de Hematología y Oncología Médica HU Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain.
Blood Coagul Fibrinolysis. 2010 Oct;21(7):632-9. doi: 10.1097/MBC.0b013e32833a9048.
The common F12 -4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 -4T allele, associated with reduced levels of FXII (P < 0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P < 0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 -4T allele. Moreover, individuals with the F12 -4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 -4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P < 0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 -4 C>T polymorphism on hemostatic tests widely used in routine clinical practice.
常见的F12 -4 C>T多态性显著调节血浆中凝血因子XII的水平，凝血因子XII是内源性凝血途径的首个要素。由于该途径在体外对血液凝固有显著影响，我们研究的目的是评估这种多态性对不同止血试验的影响。我们在566名参与者中研究了46项止血参数：280例皮肤黏膜出血患者和286名对照。与较低水平的凝血因子XII相关的F12 -4T等位基因（P < 0.001），也显著延长了以活化部分凝血活酶时间比值（aPTTr，即样本血浆/正常混合血浆的比值）表示的活化部分凝血活酶时间。因此，携带T等位基因的患者和对照均比C/C纯合个体具有更高的aPTTr（P < 0.001）。有趣的是，aPTTr延长的健康对照中有92%携带F12 -4T等位基因。此外，使用低组织因子浓度和明确接触相激活的试验，携带F12 -4T等位基因的个体也具有较少的凝血酶生成（通过内源性凝血酶潜力、凝血酶峰值和达到凝血酶峰值的时间来评估）。最后，携带F12 -4T等位基因的患者和对照的FIXc和FVIIc水平也均显著低于C/C个体（P < 0.01）。除FVIIc外，所有关联均观察到基因剂量效应，纯合TT个体的数值偏离最远。我们的研究揭示了F12 -4 C>T多态性对常规临床实践中广泛使用的止血试验有显著影响。
