Platelet glycoprotein [GPIIIA] gene polymorphism and aspirin resistance in patients with cerebrovascular accidents

ABSTRACT

Several large clinical trials have found that 30% to 40% of patients who had stroke were taking ASA at the time of their event. Several theories have been studied which offer possible explanation for aspirin resistance. A common T/C polymorphism at position 1565 in exon 2 of the GPIIIa gene has been implicated in increased prevalence of thrombosis and decreased responsiveness to aspirin. The aim of this study was to determine GPIIIa genotype and the degree of platelet activation in Egyptian patients with clinical aspirin resistance as evidenced by occurrence of cerebrovascular stroke in spite of taking aspirin for primary or secondary prevention using soluble P-selectin as a measure for the degree of platelet activation. Twenty nine patients with cerebrovascular stroke were enrolled from Kasr Eleini Hospital between Feb. 2006 and Jan. 2007. The enrollment criteria included documented ischemic stroke by radiological evidence [CT or MRI brain] in spite of regular aspirin use for the last month [75-325mg]. Twenty nine apparently healthy volunteers who are age and sex matched served as control. They were taking no medications. All patients and the control were subjected to clinical examination and routine labs for the estimation of blood sugar, lipid profile in addition to P-selectin level and determination of platelet glycoprotein IIIa T/C gene polymorphism. A significant difference was found in the frequency of GPIIIa gene polymorphism between patients and control; PL[A1A2] present in [55.1%] of patients and [17.2%] of control with odds ratio 5.9 CI95% 1.7-19.8 There was only one patient with PL[A1A2] genotype. The prevalence of PL[A1A2] in females was significantly higher 90% [9/10] than males 36.8% [7/19] [p 0.007] Odds ratio 15.4 [CI 95%1.13-53.62]. P-selectin levels were not significantly different between patients and control when done on the groups as a whole; however, when the groups were compared according to their platelet glycoprotein Ilia gene T/C polymorphism. Significant difference was found between groups, higher levels of P selectin was associated with GPIIIa gene polymorphism. P-selectin level was significantly higher in the heterozygous PL[A1]/ PL[A2] group of patients than homozygous PL[A1]/ PL[A2] group [p 0.000]. P-selectin was significantly lower in homozygous PL[A1]/ PL[A1] patients than in homozygous PL[A1]/ PL[A2] control [p 0.000] which may indicate better and partial, though not enough, response to aspirin. These findings indicate that patients who carry PLA2allele are less aspirin sensitive. In conclusion, aspirin prophylaxis should be individualized, taking the genotype, sex and cholesterol level in consideration. Further larger and prospective studies are needed to decide the optimal dose in variable conditions and the best test/s for follow-up of the effect of the drug