Increased factor VIII coagulant activity levels in male carriers of the factor V R2 polymorphism.
A common factor V gene haplotype, the FVR2 haplotype (FVHR2), has been associated with a reduced cofactor activity in activated protein C-mediated activated factor VIII inactivation. Our aim was to investigate the role of FVHR2 as a possible determinant of factor VIII levels in a population study. A total of 516 individuals (401 men, 115 women; mean age 58.4 +/- 10.8 years) were enrolled within the frame of a regional cardiovascular survey, characterized for factor VIII coagulant activity (FVIII:c) and factor V coagulant activity (FV:c) levels, and genotyped for factor V polymorphisms. In men without signs of overt inflammation, FVHR2 carriers had higher levels of FVIII:c than noncarriers (154 IU/dl, 95% confidence interval = 143-166 versus 142 IU/dl, 95% confidence interval = 138-147; P = 0.045) and were more represented in individuals with high (> or = 150 IU/dl) FVIII:c levels (21.2 versus 10.8%; odds ratio = 2.27, 95% confidence interval = 1.17-4.39 after adjustment for age, blood group and high-sensitivity C-reactive protein levels). In conclusion, this clinical report suggests the common FVHR2 as a possible independent determinant of FVIII:c levels. The report concomitantly addresses the relationship between factor V and factor VIII levels and supports the hypothesis of a mild prothrombotic role of FVHR2 by means of increased factor VIII levels.
Martinelli
Nicola
N
Department of Clinical and Experimental Medicine, University of Verona, Italy. trentinik@jumpy.it
Girelli
Domenico
D
Ferraresi
Paolo
P
Olivieri
Oliviero
O
Lunghi
Barbara
B
Manzato
Franco
F
Corrocher
Roberto
R
Bernardi
Francesco
F
D000368:Aged; D001777:Blood Coagulation; D003625:Data Collection; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D005169:Factor VIII / Q000032:analysis* / Q000502:physiology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D019851:Thrombophilia / Q000097:blood
D005165:Factor V; D005169:Factor VIII