Heritability of plasma concentrations of clotting factors and measures of a prethrombotic state in a protein C-deficient family.
BACKGROUND
Earlier studies found strong support for a genetic basis for regulation of coagulation factor levels and measures of a prethrombotic state (d-dimer, prothrombin fragment 1.2).


OBJECTIVE
Estimation of how much of the variation in the levels of coagulation factors and measures of a prethrombotic state, including measures of protein C activation and inactivation, could be attributed to heritability and household effect.


METHODS
Blood samples were collected from 330 members of a large kindred of French-Canadian origin with type I protein C deficiency. Heritability and common household effect were estimated for plasma concentrations of prothrombin, factor (F)V, factor VIII, factor (F)IX, fibrinogen, von Willebrand factor (VWF), antithrombin, protein C, protein S, protein Z, protein Z-dependent protease inhibitor (ZPI), fibrinopeptide A (FPA), protein C activation peptide (PCP), activated protein C-protein C inhibitor complex (APC-PCI), activated protein C-alpha1-antitrypsin complex (APC-alpha1AT), prothrombin fragment 1.2 (F1.2) and d-dimer, using the variance component method in sequential oligo-genic linkage analysis routines (SOLAR).


RESULTS
The highest heritability was found for measures of thrombin activity (PCP and FPA). High estimates were also found for prothrombin, FV, FIX, protein C, protein Z, ZPI, APC-PCI and APC-alpha1AT. An important influence of shared household effect on phenotypic variation was found for VWF, antithrombin, protein S and F1.2.


CONCLUSIONS
We found strong evidence for the heritability of single coagulation factors and measures of a prethrombotic state. Hemostatic markers with statistically significant heritability constitute potential targets for the identification of novel genes involved in the control of quantitative trait loci.
Vossen
C Y
CY
Pathology, University of Vermont, Burlington, VT 05405, USA.
Hasstedt
S J
SJ
Rosendaal
F R
FR
Callas
P W
PW
Bauer
K A
KA
Broze
G J
GJ
Hoogendoorn
H
H
Long
G L
GL
Scott
B T
BT
Bovill
E G
EG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000032:analysis / Q000235:genetics*; D001798:Blood Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005191:Family Characteristics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020151:Protein C Deficiency / Q000097:blood / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*
D001779:Blood Coagulation Factors; D001798:Blood Proteins