Genetics of platelet receptor single-nucleotide polymorphisms: clinical implications in thrombosis

Several single-nucleotide polymorphisms (SNPs) of platelet receptors have been implicated to be associated with an increased risk of arterial thrombosis; this review focuses on the mechanisms and the clinical significance of two specific single-nucleotide polymorphisms, ie the GP IIIa L33P (=PlA1/2) and the GP Ia 807 C/T. Whereas the mechanism of P1A2 is thought to result from 'gain of receptor function' (and there is still considerable controversy on this subject), the collagen receptor SNP is associated with an increased number of receptors on the platelet surface, thus offering a plausible explanation for the observed increased interaction with collagen and the increased risk of thrombotic events reported in some studies but not in others. Overall, the presently available (controversial) data do still not allow the conclusion that the GPIIIa polymorphism alone represents a cardiovascular risk factor in the general population. A number of mechanisms and a series of studies suggest, however, that it may be a risk factor in certain subgroups of patients or in a number of clinical situations. The GPIa SNP discussed seems to be a mild risk factor that is particularly important in synergism with known risk factors, such as smoking, hypertension, diabetes or proteinuria, etc, which may enhance its contribution to the overall cardiovascular risk.