A genetic basis for the interrelation of coagulation factors.
BACKGROUND
Evidence found in the literature for a strong correlation between coagulation factors suggests that single genes might influence the plasma concentrations of multiple coagulation factors (i.e. pleiotropically acting genes).


OBJECTIVE
To determine whether there is a genetic basis for the correlation among coagulation factors by assessing the heritability of interrelated coagulation factors.


METHODS
We performed principal components analysis, and subsequently variance components analysis, to estimate the heritability of principal components of coagulation factors in family members of a large French-Canadian kindred.


RESULTS
Four clusters were identified by principal components analysis in 200 family members who did not carry the protein C 3363C mutation. Cluster 1 consisted of prothrombin, factor VII (FVII), FIX, FX and protein S; cluster 2 consisted of FV, FIX, protein C and tissue factor pathway inhibitor; cluster 3 consisted of FVIII and von Willebrand factor; and cluster 4 consisted of antithrombin, protein C and FVII. The heritability of the principal components estimated by variance components analysis was, respectively, 37%, 100%, 37%, and 37%.


CONCLUSIONS
Our findings support the hypothesis that genes can influence plasma levels of interrelated coagulation factors.
Vossen
C Y
CY
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
Callas
P W
PW
Hasstedt
S J
SJ
Long
G L
GL
Rosendaal
F R
FR
Bovill
E G
EG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000235:genetics*; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008875:Middle Aged; D005810:Multigene Family; D009154:Mutation; D011486:Protein C / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D011863:Radioimmunoassay
D001779:Blood Coagulation Factors; D011486:Protein C; D011516:Prothrombin