Thromb Haemost 1998; 80(04): 561-565
DOI: 10.1055/s-0037-1615420
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Analysis of the F8 Gene in Individuals with High Plasma Factor VIII:C Levels and Associated Venous Thrombosis

E. P. G. Mansvelt*
,
M. Laffan
2   From the Department of Haematology, ICSM, London, UK
,
J. H. McVey
1   From the Haemostasis Research Group, MRC Clinical Sciences Centre, ICSM, London, UK
,
E. G. D. Tuddenham
1   From the Haemostasis Research Group, MRC Clinical Sciences Centre, ICSM, London, UK
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Publikationsverlauf

Received 06. April 1998

Accepted after revision 05. Juni 1998

Publikationsdatum:
08. Dezember 2017 (online)

Summary

High FVIII:C levels have previously been shown to be an independent risk factor for thrombosis with 4.8 times higher potential risk of thrombosis in individuals with FVIII:C levels greater than 1.5 u/ml. Recently, we found that raised FVIII:C levels are largely attributable to elevated FVIII:Ag levels. The determinants of FVIII:Ag levels are unclear and might be partly genetic. The promoter of the F8 gene has recently been characterised we therefore investigated the promoter and the 3’ terminus of the F8 gene for possible polymorphisms associated with raised FVIII:Ag levels in 62 selected individuals with a thrombotic tendency. We confirm previous reports that raised FVIII:C levels are largely attributable to an elevation in FVIII:Ag and this is also associated with elevation of vWF; non-O blood group; relatively short APTT and relatively low APC ratio. We screened 1140bp of the proximal promoter including the protein binding sites identified by DNase I footprint analysis by SSCP, however no polymorphisms were identified. Direct DNA sequence analysis of the region –542 to +165 failed to identify any sequence polymorphisms. The recently described polymorphism in the polyadenylation cleavage site in the prothrombin gene associated with increased prothrombin activity prompted us to screen the region surrounding the 3’ terminus of the F8 gene for polymorphisms but we found none.

* Present address: Dr. E. P. G. Mansvelt, Department of Haematological Pathology, Medical Faculty, University of Stellenbosch, PO Box 19063, Tygerberg, 7505, South Africa


 
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