The relevance of platelet glycoprotein GP IIb/IIIa polymorphism to anti-platelets response in acute coronary syndrome

The potential implication of P1A gene variants of GPIIIa of platelet GP IIb/IIIa as a genetic risk factor provocateur and/or a therapeutic outcome modulator to anti-platelet therapy in acute coronary syndrome (ACS) was probed. Study enrolled 22 controls and 44 ACS patients [non-ST segment elevation myocardial infarction (NSTEMI) vs ST segment elevation myocardial infarction (STEMI)]. They were risk stratified (TIMI score), sampled for genotyping and estimation of platelet aggregation, then subdivided according to add-on anti-platelet therapy into: clopidogrel or tirofiban subgroups. After 48 hours, the therapeutic outcome was assessed; clinically, pain relief or complication prevalence (symptomatic, electrocardiographic or hemorrhagic) and the investigational estimates were re-assessed. Intra-procedural evaluation of chest pain, ECG tracing and angiographic findings (number of culprit vessels, thrombus extent, TIMI flow, and myocardial blush) was reported in patients who underwent PCI. Frequency of plA2vs plA1 allele was higher in ACS patients (significant in ≤60 years/doubled in STEMI vs NSTEMI). TIMI score, stratification permitted considering P1A2 variant as independent risk factor in UA/NSTEMI subsets. This was fostered by intra-procedural finding of more stenotic and thrombotic lesions in P1A2 carriers. A lack of significant association between P1A variants and changes in platelet aggregation, debate its causal relation to P1A2 variant being an ACS risk factor. A positive correlation was observed between P1A variants and the therapeutic response outcome to both clopidogrel and tirofiban regarding platelet aggregation and relief of chest pain. Thus, P1A2 variant could be considered a genetic risk factor contributor rather than an anti-platelet therapeutic response modulator, when speaking of ACS. This awaits larger scale pharmacogenomic studies before a final statement is declared so as to individualize anti-platelet therapy to the best of its therapeutic outcome in ACS settings