Cited 12 times since 2004 (0.6 per year) source: EuropePMC American heart journal, Volume 147, Issue 1, 1 1 2004, Pages 181-186 Interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events. Boekholdt SM, Peters RJ, de Maat MP, Zwinderman AH, van Der Wall EE, Reitsma PH, Jukema JW, Kastelein JJ

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.

Am Heart J. 2004 1;147(1):181-186