Gene Linked to Increased Risk for Cerebral Venous Thrombosis

January 17, 2008 — Researchers have found a variant of a gene, previously been shown to increase peripheral venous thrombosis, that may also increase the risk for cerebral venous thrombosis (CVT).

Investigators at the University of Heidelberg, in Germany, found that a variant of factor XII (FXII) C46T gene polymorphism is more common in individuals with CVT than in healthy controls.

The case-control study found a total of 16.7% of patients with CVT had the gene variant, compared with 5.5% of controls.

"These results need to be confirmed, but it appears that people with cerebral venous thrombosis should be tested for this gene and should be considered for use of blood-thinning medications to prevent future blood clots," study author Christoph Lichy, MD, said in a statement released by the American Academy of Neurology.

The study is published in the January 8 issue of Neurology.

CVT Incidence Not Completely Explained

According to the authors, CVT accounts for approximately 0.5% of cerebrovascular disease, with an estimated mortality of about 10%.

Several thrombophilic genetic variants, including factor V Leiden (FVL) and factor II G20210A mutation (FII mutation), have been associated with the condition. However, the authors say that all the variants together do not explain the total incidence.

According to the study, reduced FXII plasma levels were found in patients with retinal and peripheral venous thrombosis (PVT) and in women with recurrent miscarriages. Furthermore, other research has linked the FXII 46TT genotype to PVT and ischemic stroke.

The study included 78 white patients with nonseptic CVT and 201 control subjects. Diagnosis of the condition was restricted to patients with pathognomonic findings on magnetic resonance imaging or conventional angiography.

The control group consisted of 201 individuals with no self-reported history of cerebrovascular disease or PVT who were randomly selected from population registries.

Practical Implications

All study participants underwent a systematic review of their clinical notes and testing for the presence of the TT genotype of the FXII C46T. In addition, control subjects underwent a standardized interview on vascular health and risk factors.

After adjusting for age, sex, oral contraceptive use, FVL and FII mutations, the researchers found the FXII TT genotype was associated with a 4.5-fold increased risk for CVT.

The investigators also found that compared with controls, more patients had an additional FVL or FII mutation, a finding that suggests there may be an additional increased risk for CVT in carriers of multiple thrombophilic genetic variants.

"If confirmed by a second independent study, our data should promote the inclusion of the FXII C46T gene polymorphism into the routine diagnostic workup of CVT," they write.

The authors report no conflicts of interest.

Neurology. 2008;70:129-132.