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 (GPIIb/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=2.2 × 10(-4)) and HPA-1b/2b (Pc=.001) haplotypes which were positively associated, and the HPA-1a/2a (Pc=3.2 × 10(-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.