HIGH PREVALENCE OF A MUTATION IN THE FACTOR-V GENE WITHIN THE UK POPULATION - RELATIONSHIP TO ACTIVATED PROTEIN-C RESISTANCE AND FAMILIAL THROMBOSIS

Recent findings have indicated the importance of factor V (FV) in caus ing resistance to activated protein C (APC) in a high proportion of pa tients with venous thrombosis. This prompted us to investigate whether resistance could be due to defective inactivation of FVa by APC. Cons equently, we amplified a 3.2 kb fragment of the FV gene sequence encod ing the heavy chain APC cleavage site. DNA analysis showed a guanine t o adenine transition at nucleotide 1691 in all affected members of two families with inherited APC resistance associated with thrombosis and confirmed suspected homozygosity in two individuals. The mutation, in heterozygous form, was also found in similar to 35% of our normal pop ulation (n = 144) and correlated with low APC resistance. The high pre valence of this mutation suggests that it may be a major contributory factor in early thrombosis.