Cooper D N, Tuddenham E G
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, UK.
Br Med Bull. 1994 Oct;50(4):833-50. doi: 10.1093/oxfordjournals.bmb.a072929.
Mutations in a variety of human genes are now known to predispose to venous thrombosis. Study of these mutations has led to important advances in our understanding of the structure and function of haemostatic regulatory proteins and has facilitated accurate presymptomatic and antenatal diagnosis. However, owing to the probabilistic nature of thromboembolism, only a certain proportion of patients with a recognized gene defect in the heterozygous state will actually suffer from thrombotic episodes. Allelic heterogeneity, epistatic effects resulting from the influence of other loci and environmental insults of various kinds all play a role in determining whether a thrombotic event occurs in individuals already compromised by a gene defect. Nevertheless, characterization of the wide spectrum of gene mutations giving rise to thrombosis may allow us to relate specific gene lesions to the probability of thromboembolism as well as to the severity and frequency of thrombotic episodes.
现已明确，多种人类基因的突变会使人易患静脉血栓形成。对这些突变的研究使我们在了解止血调节蛋白的结构和功能方面取得了重要进展，也有助于进行准确的症状前诊断和产前诊断。然而，由于血栓栓塞具有概率性，只有一定比例的杂合状态下存在已知基因缺陷的患者会实际发生血栓形成事件。等位基因异质性、其他基因座影响产生的上位效应以及各种环境损伤在决定基因缺陷患者是否发生血栓形成事件中均起作用。尽管如此，对导致血栓形成的广泛基因突变进行特征描述，可能使我们将特定的基因损伤与血栓栓塞的概率以及血栓形成事件的严重程度和发生频率联系起来。
