Haplotypes encoding the factor VIII 1241Glu variation, factor VIII levels and the risk of venous thrombosis

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Nossent, A.Yael and Eikenboom, Jeroen C.J. and Vos, Hans L. and Bakker, Egbert and Tanis, Bea C. and Doggen, Carine J.M. and Bertina, Rogier M. and Rosendaal, Frits R. (2006) Haplotypes encoding the factor VIII 1241Glu variation, factor VIII levels and the risk of venous thrombosis. Thrombosis and Haemostasis, 95 (6). pp. 917-1051. ISSN 0340-6245

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Abstract:Levels of factorVIII (FVIII) are associated with the risk of venous thrombosis.The FVIII variation D1241E has been reported to be associated with decreased levels of FVIII. Our objective was to study whether D1241E is associated with levels of FVIII and the risk of venous thrombosis and whether this association is caused by D1241E or another linked variation.We analyzed the association of three FVIII gene haplotypes encoding 1241E (further denoted as HT1, HT3, and HT5) with FVIII levels and thrombosis risk. This analysis was performed in the Leiden Thrombophilia Study (LETS). The control populations of two case-controls studies on arterial thrombosis in men and women, respectively, were used to confirm the effects observed on FVIII:C in the LETS.In men,HT1 was associated with a 6% re- duction in FVIII:C and with a reduced risk of venous thrombosis [odds ratio 0.4 (CI95 0.2–0.8)]. Logistic regression showed that the risk reduction was only partially dependent of the reduction in FVIII levels. HT1 showed no effects in women on either FVIII:C or risk of thrombosis.The number of carriers of HT3 and HT5 was too low to make an accurate estimate of the risk of venous thrombosis. Neither HT3 nor HT5 showed effects on levels of FVIII:C.When we consider that all three haplotypes encoding 1241E show different effects on FVIII:C and thrombosis risk, it is possible that D1241E is not the functional variation. However, FVIII gene variations do contribute to both levels of FVIII and the risk of thrombosis
Item Type:Article
Copyright:© 2006 Schattauer Publishers
Link to this item:http://purl.utwente.nl/publications/77891
Official URL:http://dx.doi.org/10.1160/TH06-01-0024
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