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 Arg506 in the APC cleavage site to a Gln was found in APC resistant individuals. These results suggest factor V gene mutation to be the most common genetic cause of thrombophilia.
Zöller
B
B
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Dahlbäck
B
B
D000483:Alleles; D001120:Arginine / Q000737:chemistry; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D005165:Factor V / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011486:Protein C / Q000235:genetics*; D018455:Protein S Deficiency; D011863:Radioimmunoassay; D013924:Thrombophlebitis / Q000235:genetics*
D017931:DNA Primers; D011486:Protein C; D005165:Factor V; D004247:DNA; D001120:Arginine