DOI: 10.5176/2251-2489_BioTech13.34
Authors: Omnia Nayel1, Mohamed Sobhy, Azza Baraka, Mohamed El Samak and Sherine Abdel Kader
Abstract:
The era of pharmacogenomics is intervening in cardiovascular therapeutic armamentarium. In this respect, the potential implication of PlA gene variants of GPIIIa subunit of platelet membrane GP IIb/IIIa as a genetic risk factor provocateur and/or as a therapeutic outcome modulator to anti-platelet therapy in ACS was of current interest. In this case-control study 22 controls and 44 ACS patients (NSTEMI vs STEMI) were recruited and subjected to risk stratification using TIMI score and blood sampling [for genotyping to detect polymorphism in GPIIIa subunit and for estimation of platelet aggregation and malondialdehyde (MDA) level (a marker of oxidative injury), aside the routine laboratory testing]. Patients were further subdivided a*ccording to the add-on anti-platelet therapy used into: a clopidogrel (loading oral dose of 300 mg (4 tablets), followed by 75 mg once daily) or a tirofiban (0.4 g/ kg/ min. for 30 minutes IV infusion, followed by a maintenance infusion of 0.1 g/ kg/ min. for 48-72 hours) subgroups. After 48 hours of hospitalization, the therapeutic outcome was assessed clinically in terms of freedom from chest pain and presence or absence of complications (recurrence of chest pain, ECG changes, bleeding or re-infarction). The investigational estimates were also re-assessed by the end of the 48 hours. A further intra-procedural evaluation of chest pain, ECG tracing and angiographic findings (extent of thrombus, TIMI flow and myocardial blush) was reported only to patients who underwent PCI. Results cleared that frequency of PlA2 vs PlA1 allele was lower in controls and higher in ACS patients (significant in elder > 60 years and doubled in STEMI vs NSTEMI). Stratification findings of TIMI score, permitted considering PlA2 variant as an independent risk factor particularly in UA/NSTEMI subset of ACS patients. This was fostered by finding more stenotic and thrombotic lesions in PlA2 carriers during intra-procedural evaluation. However, the lack of any significant association between PlA variants and changes in platelet aggregation or oxidative injury, rules out their causal relation to stand behind PlA2 variant being an ACS risk factor. Meanwhile, a positive correlation was observed between PlA variants and the therapeutic response outcome to both clopidogrel and tirofiban regarding platelet aggregation and relief of chest pain while their antioxidative potentiality was negatively correlated only to PlA1 carriers. In conclusion, the PlA2 variant could be considered more as a genetic risk factor contributor than an anti-platelet therapeutic response modulator when speaking of ACS. This awaits larger scale pharmacogenomic studies before a final statement is declared.
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