Haemostatic gene polymorphisms in venous and arterial thrombosis

Abstract

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.