LINKAGE BETWEEN INHERITED RESISTANCE TO ACTIVATED PROTEIN-C AND FACTOR-V GENE MUTATION IN VENOUS THROMBOSIS

Resistance to activated protein C (APC) is a major cause of familial thrombophilia, and can be corrected by an anticoagulant activity expressed by purified factor V. We investigated linkage between APC resistance and the factor V gene in a large kindred with familial thrombophilia. Restriction fragment length polymorphisms in exon 13 of the factor V gene were informative in 14 family members. The 100% linkage between factor V gene polymorphism and APC resistance strongly suggested a factor V gene mutation as a cause of APC resistance. A point mutation changing Arg(506) in the APC cleavage site to a Gin was found in APC resistant individuals. These results suggest factor V gene mutation to be the most common genetic cause of thrombophilia.