Lane David A, Mollica Luigina R
Department of Haematology, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital Campus, London, UK.
Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):213-5. doi: 10.1159/000073568.
Haemostatic gene polymorphisms are potential risk factors for thrombosis. Considerable attention has been focussed on identifying risk alleles. Progress has undoubtedly been made in venous thrombosis. Factor V Leiden and the prothrombin G20210A substitution are now established risk factors, and a number of other polymorphisms are candidates. The initial promise that genetic risk factors might contribute appreciably to an explanation of the development of arterial thrombotic disorders has largely been unfulfilled and the expectations raised by early reports of positive associations have been tempered by inconsistent results with almost all genes studied. The problems seen in arterial disease are replicated in investigations of other complex diseases. In the optimistic rush to show positive associations of genetic factors with diseases, sight has been lost of the need for stringent study design. Furthermore, the scale of studies needed to produce reproducible conclusions has been underestimated. The lessons learnt from accumulated experience should now enable progress to be made.
止血基因多态性是血栓形成的潜在危险因素。人们已将大量注意力集中在识别风险等位基因上。在静脉血栓形成方面无疑已取得进展。因子V莱顿突变和凝血酶原G20210A替代现在已被确认为风险因素，还有许多其他多态性也有可能。遗传风险因素可能对解释动脉血栓性疾病的发生有显著贡献这一最初的希望在很大程度上并未实现，早期关于阳性关联的报告所引发的期望因几乎所有研究基因的结果不一致而有所缓和。在动脉疾病中看到的问题在其他复杂疾病的研究中也有出现。在急于展示遗传因素与疾病的阳性关联的乐观情绪中，人们忽略了严格研究设计的必要性。此外，得出可重复结论所需的研究规模被低估了。从积累的经验中学到的教训现在应能推动取得进展。
