title: Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C.
abstract: Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.
authors.affiliation: Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Zöller
authors.forename: P J
authors.initials: PJ
authors.lastname: Svensson
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: B
authors.initials: B
authors.lastname: Dahlbäck
mesh_terms: D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D004351:Drug Resistance / Q000235:genetics; D004789:Enzyme Activation; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D011486:Protein C / Q000494:pharmacology*; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology; D013924:Thrombophlebitis / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011486:Protein C; D005973:Glutamine; D005165:Factor V; D001120:Arginine