title: The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.
authors.affiliation: Department of Clinical Medicine, Cardiovascular and Immunologic Sciences, Federico II University School of Medicine, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Galasso
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
authors.forename: Federico
authors.initials: F
authors.lastname: Piscione
authors.forename: Roberta
authors.initials: R
authors.lastname: De Rosa
authors.forename: Valentina
authors.initials: V
authors.lastname: Trimarco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Piccolo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cassese
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
mesh_terms: D000368:Aged; D000483:Alleles; D050197:Atherosclerosis; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D003328:Coronary Thrombosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics* / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D039302:Integrin alphaVbeta3; D039661:Integrin beta3