Epg. Mansvelt et al., ANALYSIS OF THE F8 GENE IN INDIVIDUALS WITH HIGH PLASMA FACTOR VIII-CLEVELS AND ASSOCIATED VENOUS THROMBOSIS, Thrombosis and haemostasis, 80(4), 1998, pp. 561-565
High FVIII:C levels have previously been shown to be an independent ri
sk factor for thrombosis with 4.8 times higher potential risk of throm
bosis in individuals with FVIII:C levels greater than 1.5 u/ml. Recent
ly, we found that raised FVIII:C levels are largely attributable to el
evated FVIII:Ag levels. The determinants of FVIII:Ag levels are unclea
r and might be partly genetic. The promoter of the F8 gene has recentl
y been characterised we therefore investigated the promoter and the 3'
terminus of the F8 gene for possible polymorphisms associated with ra
ised FVIII:Ag levels in 62 selected individuals with a thrombotic tend
ency. We confirm previous reports that raised FVIII:C levels are large
ly attributable to an elevation in FVIII:Ag and this is also associate
d 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 an
alysis by SSCP, however no polymorphisms were identified. Direct DNA s
equence analysis of the region -542 to +165 failed to identify any seq
uence polymorphisms. The recently described polymorphism in the polyad
enylation cleavage site in the prothrombin gene associated with increa
sed prothrombin activity prompted us to screen the region surrounding
the 3' terminus of the F8 gene for polymorphisms but we found none.