Blood, 15 May 2001, Vol. 97, No. 10, pp. 2921-2921
Coagulation gene polymorphisms: the benefit?
Genetic polymorphisms of coagulation factors are known risk
factors for venous thrombosis (factor V Leiden, prothrombin G20210A) and candidate risk factors for arterial thrombosis. A frequently asked
question is why these polymorphisms spread so extensively throughout
the white populations when they are associated with these disabling and
potentially life threatening conditions. Are there evolutionary
advantages to be derived from a polymorphism that predisposes to
thrombotic diseases? Corral and colleagues (page 2979) have
investigated 201 patients with verified intracranial bleeding for the
prevalence of 4 coagulation gene polymorphisms. While the prevalences
of factor V Leiden, prothrombin G20210A, factor VII 
323del and factor
XIII V34L were those expected in the 2 control populations used, the
first 3 polymorphisms were underrepresented in the patients. This
suggests a benefit in being a polymorphism carrier, having protection
against acquired hemorrhage.
It will be important to confirm this work with independent
investigations, particularly as studies of genetic variation are prone
to bias arising from admixtures, stratification, and patient selection.
Additionally, even in initially large genetic studies, crucial
comparison groups inevitably become small. It should also not be
forgotten that polymorphisms do not directly alter disease but must act
through a phenotype. When confirmation is sought of these
interesting findings, the role of the clotting
factors/intermediate phenotypes involved must also be explored, as
the analysis of these might be equally rewarding. It is too early to
speculate whether and how these findings might be translated into
clinical practice: it is sobering that there is as yet not a clear
patient management use for factor V Leiden in thrombosis. But the
results do suggest an explanation for the presence of functional
polymorphisms in coagulation genes and remind us of the delicate nature
of the hemostatic balance. Furthermore, they suggest that evaluation of
polymorphisms in fibrinolytic and platelet receptor genes in acquired
bleeding will also be informative.
David Lane
Imperial College School of
Medicine
