Interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events.
BACKGROUND
The PlA1A2 polymorphism of glycoprotein IIIa (GPIIIa), which affects postoccupancy signaling by the platelet fibrinogen receptor IIbIIIa, has been investigated as a potential genetic risk factor for cardiovascular events in numerous studies, without consistent results. We investigated whether the effect of this genetic variant of the platelet fibrinogen receptor on the risk of cardiovascular events is affected by fibrinogen plasma levels.


METHODS
The GPIIIa PlA1A2 polymorphism and fibrinogen levels were determined in 455 men with angiographically documented coronary atherosclerosis.


RESULTS
Neither carriership of the rare PlA2 allele nor fibrinogen plasma levels affected the time to cardiovascular event, as assessed in a proportional hazards model. However, there was a significant interaction between PlA2 carriership and fibrinogen plasma levels (P =.002). Carriership of the variant PlA2 allele significantly affected event-free survival only in individuals within the highest fibrinogen quartile (hazard ratio, 2.7; 95% CI, 1.1 to 7.1; P =.03).


CONCLUSIONS
We observed a statistically significant interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events. This interaction may account for the inconsistent results of genetic association studies investigating this genotype as a genetic risk factor in thrombotic cardiovascular events.
Boekholdt
S Matthijs
SM
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Peters
Ron J G
RJ
de Maat
Moniek P M
MP
Zwinderman
Aeilko H
AH
van Der Wall
Ernst E
EE
Reitsma
Pieter H
PH
Jukema
J Wouter
JW
Kastelein
John J P
JJ
D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy; D018572:Disease-Free Survival; D005340:Fibrinogen / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011859:Radiography; D039341:Receptors, Fibrinogen / Q000235:genetics*; D018570:Risk Assessment
D039661:Integrin beta3; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D039341:Receptors, Fibrinogen; D005340:Fibrinogen; D017035:Pravastatin