Polymorphisms of human platelet alloantigens HPA-1 and HPA-2 associated with severe coronary artery disease

Objectives: Insofar as platelet membrane glycoprotein (GP) polymorphisms were identified as potential risk factors for coronary artery disease (CAD), we investigated the contribution of human platelet antigen (HPA)-1 (GPIlb/IIIa) and HPA-2 (GPIb/IX) alleles and haplotypes to CAD pathogenesis. Methods: Study subjects comprised 247 middle-age CAD patients and 316 age-, gender-, and race-matched controls; HPA genotyping was performed by polymerase chain reaction with sequence specific primers. Results: The frequencies of HPA-1b (P<.001) and HPA-2b (P<.001) alleles and HPA-1a/1b (P<.001), HPA-1b/1b (P<.001), and HPA-2a/2b (P<.001) genotypes were higher in patients than control subjects. Select HPA haplotypes comprising the HPA-1b/2a (Pc=2.2x10(-4)) and HPA-1b/2b (Pc=.001) haplotypes which were positively associated, and the HPA-1a/2a (Pc=3.2x10(-5)) which was negatively associated with CAD, confer a disease susceptibility and protective nature to these haplotypes. Multivariate analysis confirmed the positive association of HPA-1b/2a [adjusted odds ratio (aOR)=3.63; 95% CI=2.42-5.43] and HPA-1b/2b (aOR=2.92; 95% CI=1.43-5.94) haplotypes with CAD, after adjustment for a number of covariates. Conclusions: Our results suggest that HPA-1/HPA-2 haplotypes may be considered to be a major risk factor for CAD in middle-aged Tunisians. (C) 2010 Elsevier Inc. All rights reserved.