The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events

Abstract

BackgroundThe clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.MethodsWe studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.ResultsThe frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).ConclusionsOur study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.

Genetic risk factors of atherothrombosis

“…They also observed that the overall OR for adverse outcome after revascularization procedures was 1.31 (95% CI, 1.10-1.56). 66 In agreement with these results, Galasso et al 67 demonstrated that the PLA2 allele is associated with thrombotic cardiovascular complications in 400 consecutive patients with CAD undergoing percutaneous coronary intervention. Moreover, the combination of the PLA2 allele of GPIIIa and the 807T allele of GPIa was found to confer additional risk for the development of carotid atherosclerosis and arterial thrombosis in patients with type 2 diabetes.…”

Common Genetic Variants in Platelet Surface Receptors and its Association with Ischemic Stroke

“…In a previous study, a higher frequency of A2 allele was observed in patients with large-vessels stroke [39]. The PIA2 allele was also an independent ischemic stroke risk factor in Caucasian women and in a hypertensive Caucasian population [33,40,41]. In line with this, Maguire et al found an association between GPIIIa rs5918 and the Barthel Index score that followed a dominant model but this association was not significant for the modified Rankin Scale and the Glasgow Outcome Scale scores [42].…”

The association of ITGB3 gene and NOS3 gene with the severity of coronary artery disease with and without type 2 diabetes

“…Ожирение также является значимым фактором риска прогресси-рования и ИБС, и СД2. Кроме того, указывается на со-пряженность аллеля 1565C гена ITGB3 с низким порогом активации тромбоцитов и их повышенной агрегацией, что обусловливает более высокий риск неблагоприятных сердечно-сосудистых событий [6,8].…”

“…Носительство аллеля 1565C сопряжено с высоким ри-ском развития инфаркта миокарда (ИМ), агрессивным протеканием атеротромботической болезни и более вы-сокой смертностью [7,8]. Полиморфизм T-786C гена NOS3, а именно аллель 786С определяет меньшую ак-тивность фермента eNOS и, следовательно, сниженный синтез NO, что предрасполагает к более длительному коронароспазму [9].…”