Platelet glycoprotein IIIa Pl(A) polymorphism, fibrinogen, and platelet aggregability - The Framingham heart study

Background-Recent data suggest that the Pl(A2) allele of the platelet glyco protein IIIa receptor may be a genetic risk factor fur cardiovascular disea se. We previously reported that the Pl(A2) allele was associated with incre ased platelet aggregability, as indicated by lower epinephrine threshold co ncentrations. Paradoxically, however, it has been reported that Pl(A2)-posi tive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with PP genotype in modulating platelet aggregability, Methods and Results-Glycoprotein ma PIA genotype, fibrinogen level, and pla telet aggregability were ascertained in 1340 subjects enrolled into the Fra mingham Offspring Study. Platelet aggregability was evaluated by the Barn m ethod. Higher fibrinogen levels were associated with increased epinephrine- induced aggregation (P=0.002) and a trend for ADP-induced aggregation (P=0. 07). The fibrinogen effect was genotype specific, however, in that the incr ease in platelet aggregability with higher fibrinogen was present for the p l(A1/A1) genotype (P=0.0005 and P=0.03 for epinephrine- and ADP-induced agg regation respectively) but not for the Pl(A2)-positive genotype (P >0.90). Conclusion-Higher fibrinogen levels were associated with increased platelet aggregability, However, the association between fibrinogen and platelet ag gregability was genotype specific. This interaction may be responsible for the conflicting findings regarding PIA genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight int o cardiovascular disease risk.