Interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events

Background The PIA1A2 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 PIA1A2 polymorphism and fibrinogen levels were determined in 455 men with angiographically documented coronary atherosclerosis. Results Neither carriership of the rare PIA2 allele nor fibrinogen plasma levels affected the I time to cardiovascular event, as assessed in a proportional hazards model. However, there was a significant interaction between PIA2 carriership and fibrinogen plasma levels (P = .002). Carriership of the variant PIA2 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.