Heritability of platelet function in families with premature coronary artery disease.
BACKGROUND
Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.


METHODS
Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.


RESULTS
Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h(2)) for epinephrine- and adenosine diphosphate-induced aggregation (0.36-0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47-0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 muM epinephrine, but the effect differed by race.


CONCLUSIONS
Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology.
Jefferson College of Medicine, Philadelphia, PA, USA. paul.bray@jefferson.edu
P F
PF
Bray
R A
RA
Mathias
N
N
Faraday
L R
LR
Yanek
M D
MD
Fallin
J E
JE
Herrera-Galeano
A F
AF
Wilson
L C
LC
Becker
D M
DM
Becker
D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000208:ethnology; D005192:Family Health; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000150:complications / Q000175:diagnosis; D013929:Thromboxane B2 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D013929:Thromboxane B2; D005340:Fibrinogen