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20-09-2010 | Cardiology | Article

Association between TFPI polymorphisms and VTE risk unclear


Free abstract

MedWire News: Polymorphisms in the tissue factor pathway inhibitor type 1 gene (TFPI) modify the expression of its protein, which may in turn increase the risk for venous thromboembolism (VTE), according to Norwegian researchers.

The TFPI protein plays a major role in regulating the initiation of coagulation, and low TFPI levels have been associated with an increased risk for VTE, explain Per Morten Sandset (Oslo University Hospital) and colleagues.

In the present study, Sandset and team investigated the influence of TFPI polymorphisms on plasma TFPI levels.

They assessed the frequency of four polymorphisms (-287T/C and -399C/T in the 5' upstream region, -33T/C in intron 7 and 874G/A in exon 9) in postmenopausal women with a history of venous thrombosis (n=138), in healthy postmenopausal women participating in a study of hormone therapy (n=202), and female blood donors (n=212).

The researchers found no significant differences in the frequency of the polymorphisms between women with and without a history VTE.

Carriers of -287C (hetero- and homozygotes combined) had marginally higher levels of TFPI-free antigen compared with women homozygous for -287T, at 15.6 versus 14.8 ng/ml.

In addition, TFPI activity, but not TFPI-free antigen, was lower among carriers of the -399T variant (hetero- and homozygotes combined), and higher among carriers of the -33C variant compared with carriers of the -399C and -33T variants, respectively.

Of note, TFPI-free antigen levels were significantly reduced by approximately 25% among women taking conventional-dose hormone therapy, compared with placebo, irrespective of genotype.

However, this effect was less pronounced among healthy postmenopausal women treated with low-dose hormone therapy who carried the -287C variant, suggesting a slightly reduced VTE risk in these individuals, the researchers write.

"Our results suggest that some polymorphisms in the TFPI gene may affect plasma TFPI levels, and thereby potentially modify the risk for VTE," conclude Sandset and co-authors in the journal Blood Coagulation and Thrombolysis.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Laura Dean

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