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A Possible New Genetic Risk Factor for Cerebral Venous Thrombosis

Homozygosity for the factor XII C46T polymorphism is associated with increased risk for cerebral venous sinus thrombosis.

The C46T polymorphism of factor XII has been associated with decreased levels of factor XII (Thromb Res 2001; 101:255), and clinical evidence suggests that deficiencies may be associated with heightened risk for venous thrombosis. However, this factor activates both thrombosis and fibrinolysis, and deficiencies have also been associated with protection from acute coronary syndrome (J Thromb Haemost 2007; 5:700 and Br J Haematol 2001; 115:1007). In this case-control study, the authors investigated the association between the factor XII C46T polymorphism and cerebral venous thrombosis (CVT). They compared the prevalences of the TT polymorphism of C46T among 78 patients with CVT and among 201 healthy controls from South Germany.

The TT genotype was significantly more common among the patients with CVT than among controls (16.7% vs. 5.5%; univariate odds ratio, 2.90). Correction for known risk factors suggested a strong independent association (adjusted OR, 4.57). CVT patients were also more likely than controls to carry one of the other genetic lesions known to increase CVT risk (factor V Leiden and the prothrombin gene FIIG20210A), suggesting a cumulative effect on risk. The authors conclude that the homozygous genotype for factor XII C46T may be a newly identified independent risk factor for CVT.

Comment: Although preliminary, these findings suggest that we may have found another important genetic risk factor for cerebral venous thrombosis. The TT genotype occurs in 5% to 7% of white people (Thromb Res 2001; 101:255), comparable to factor V Leiden (about 5%–8%) and greater than FIIG20210A (about 2%), making it a potentially important addition to the diagnostic evaluation of patients with CVT. However, given the dual effects of factor XII, it remains possible that low levels can either cause or protect against thrombosis. Therefore, this finding should encourage further study of the role of this polymorphism in CVT.

— Steven Feske, MD

Dr. Feske is Director, Stroke Division, Department of Neurology, Brigham and Women’s Hospital, Boston.

Published in Journal Watch Neurology March 11, 2008

Citation(s):

Reuner KH et al. Factor XII C46T gene polymorphism and the risk of cerebral venous thrombosis. Neurology 2008 Jan 8; 70:129.

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