Activation markers of coagulation and fibrinolysis in twins:: heritability of the prethrombotic state
Activation markers of coagulation and fibrinolysis in twins:: heritability of the prethrombotic state
复制标题
DOI：
10.1016/s0140-6736(02)07813-3
复制
发表时间：
2002-02-23
期刊：
影响因子：
168.9
通讯作者：
Grant, PJ
中科院分区：
文献类型：
--
作者：
Ariëns, RAS;de Lange, M;Grant, PJ
背景：在冠状动脉疾病和其他血栓性疾病的危险个体中，凝血和纤溶的激活标志物增加--这种情况被定义为血栓前状态。方法采用双抗体夹心酶联免疫吸附试验(EL ISA)检测118对21~73岁同卵双生子和112对异卵双生子的凝血酶原、凝血酶原片段1+2、凝血酶-抗凝血酶复合体、交联型纤维蛋白降解产物D-二聚体和凝血酶激活纤溶抑制物的浓度。我们使用定量遗传模型拟合来估计遗传力。我们发现血浆中激活标志物的浓度具有显著的遗传力。遗传因素分别贡献了片段1+2、凝血酶-抗凝血酶复合体和D-二聚体浓度变化的45%、40%和65%。年龄只在片段1+2浓度中重要，在片段1+2浓度中，年龄占变异的12%。其余的变化可能归因于独特的环境因素。血浆中前体凝血酶原浓度的变化由57%的遗传力决定，而酶原凝血酶激活的纤溶抑制物的浓度显示出很强的遗传成分(82%)。说明凝血和纤溶系统的激活机制，因此血栓前状态，在很大程度上是由遗传因素控制的。在普通人群中，影响止血活性的基因可能是总体血栓形成倾向的重要组成部分。
Background Activation markers of coagulation and fibrinolysis are increased in individuals at risk of coronary-artery disease and other thrombotic disorders-a condition defined as the prethrombotic state. We aimed to find out the extent to which the prethrombotic state is determined by genetic factors.Methods We analysed concentrations of prothrombin, prothrombin fragment 1+2, thrombin-antithrombin complex, crosslinked fibrin degradation product D-dimer, and thrombin-activatable fibrinolysis inhibitor by ELISA in 118 monozygotic and 112 dizygotic unselected female twins aged 21-73 years from the St Thomas' UK Adult Twin Registry. We used quantitative genetic-model fitting to estimate heritability.Findings We found significant heritabilities in concentrations of the activation markers in plasma. Genetic factors contributed 45, 40, and 65% of the variation in concentrations of fragment 1+2, thrombin-antithrombin complex, and D-dimer, respectively. Age was important only in fragment 1+2 concentrations, in which it accounted for 12% of the variation. The remaining variation could be attributed to unique environmental factors. Variation in concentrations of precursor prothrombin in plasma was determined by 57% heritability, and that of zymogen thrombin-activatable fibrinolysis inhibitor showed a very strong genetic component (82%).Interpretation The activation mechanisms of the coagulation and fibrinolytic systems, and therefore the prethrombotic state, are controlled to a substantial degree by genetic factors. Genes influencing activation of haemostasis are likely to be an important component of the overall thrombotic tendency in the general population.