Polymorphisms in the factor VII gene and ischemic stroke in young adults

Abstract

Polymorphic configurations of the coagulation factor VII gene (F7) are associated with plasma levels of FVII antigen (FVII:Ag) and FVII coagulant activity (FVII:C). Our aim was to determine whether F7 polymorphisms influence risk of ischemic stroke in young adults. One hundred and fifty survivors of ischemic stroke before the age of 45 and an equal number of age and sex-matched controls were genotyped for five F7 polymorphisms: the -A670C transversion, -323 decanucleotide insertion (P + 10), the number (which varies between five and eight) of a 37 base pair repeat polymorphisms in intron 7 (IVS7), amino acid substitution R353Q, and +154AA insertion. 353Q, P + 10 and +154AA were demonstrated to associate with significantly decreased plasma FVII:Ag, whereas -670C and IVS7 seven or higher were associated with a tendency towards increased plasma FVII:Ag. The former three polymorphisms were significantly more common in control individuals than in patients, whereas the latter two were significantly more common in patients than in control individuals. The multiple logistic regression analysis revealed that two F7 polymorphisms, -670C and IVS7 seven or higher, are independent risk factors for ischemic stroke in young adult patients.

Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis

“…The allele -402 G/A has been independently associated with the increased transcriptional activity of FVII (Lopaciuk et al, 2010). The allele -401 G/T is significantly associated with lower plasma levels of FVII (Eroğlu et al, 2010).…”

“…Several studies have examined these polymorphisms in patients with venous and arterial thrombosis, but the results are very variable and sometimes contradictory (Athanasiadis et al, 2010;Lopaciuk et al, 2010;Eroğlu et al, 2010Eroğlu et al, , 2011Previtali et al, 2011;Friso et al, 2012).…”

“…Jackson et al (2000) in another case-control study of 500 unselected patients showed that the ID polymorphism in the ACE gene was not a risk factor for venous thromboembolism. Lopaciuk et al (2010) analyzed the genetic profiles of 38 patients who had a postoperative symptomatic pulmonary embolism or proximal deep venous thrombosis after arthroplasty, and 241 control subjects without thrombosis. No difference between the groups was observed.…”

“…This rupture triggers the formation of a localized blood clot, rich in activated platelets that, together with macrophages and monocytes, causes the occlusion of the vessel, preventing the normal liberation of antithrombotic agents such as nitric oxide and promoting prothrombotic substances such as tissue factor (TF). The human atherosclerotic plaque contains large amounts of tissue factor and it has been suggested that, after plaque rupture, tissue factor initiates the activation of the coagulation system that contributes to the formation of an occlusive clot (Boles and Mackman, 2010;Lopaciuk et al, 2010).…”

Thrombophilia screening in young patients with cryptogenic stroke

“…However, the majority of case-control studies demonstrated no association between predictors of venous thromboembolism and increased stroke risk (4,22). Notably, even in stroke patients with cardiac right-to-left shunt, there was no increased prevalence of thrombophilic diathesis (22,31). So far, thrombophilia work-up regarding the arterial system has been predominantly focused on the diagnosis of antiphospholipid syndrome (9).…”