The genetics of venous and arterial thromboembolism

There is substantial evidence to indicate that the pathologic processes of venous and arterial thromboembolism involve both genetic and environmental influences. Scientific progress over the past decade has revealed a growing number of genetic factors, such as factor V Leiden and the prothrombin gene variant, that are present in more than 1% of the population and increase the relative risk of venous thrombosis between two- and sevenfold. Furthermore, several of these factors have been demonstrated to interact adversely with environmental influences, such as oral contraceptives and smoking. Although these traits are present at relatively high prevalence in the population, the magnitude of the increased thrombotic risk associated with these factors is substantially less than that related to inherited deficiency of the natural anticoagulant protein antithrombin, and somewhat less than the elevated risk with protein C and protein S deficiencies. In contrast to the progress that has been made in understanding the genetic contributions to venous thromboembolism, much still remains to be learned about the genetic basis of arterial thrombosis. Despite the documentation of associations between several genetic polymorphisms with plasma procoagulant levels, consistent associations with arterial thrombotic disease have not been found.