Several single-nucleotide polymorphisms (SNPs) of platelet receptors have b
een implicated to be associated with an increased risk of arterial thrombos
is; this review focuses on the mechanisms and the clinical significance of
two specific single-nucleotide polymorphisms, ie the GP IIIa L33P (=Pl(A1/2
)) and the GP Ia 807 C/T. Whereas the mechanism of Pl(A2) is thought to res
ult from 'gain of receptor function' (and there is still considerable contr
oversy on this subject), the collagen receptor SNP is associated with an in
creased number of receptors on the platelet surface, thus offering a plausi
ble explanation for the observed increased interaction with collagen and th
e increased risk of thrombotic events reported in some studies but not in o
thers. Overall, the presently available (controversial) data do still not a
llow the conclusion that the GPIIIa polymorphism alone represents a cardiov
ascular 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 certai
n 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 car
diovascular risk.