ABSTRACT
The contribution of human platelet antigen (HPA)-1 (GPIIb/IIIa), HPA-2 (GPIb/IX), and HPA-3 (GPIIb/IIIa) polymorphisms to the risk of coronary artery disease (CAD) was investigated in 341 CAD patients and 316 matched control subjects. HPA genotyping was performed by PCR-SSP. Regression analysis was employed in assessing the contribution of these variants to CAD risk. The frequency of HPA-1b (P = .009) and HPA-3b (P = .004) alleles, and HPA-1a/1b (P = .045), HPA-1b/1b (P = .007), and HPA-3b/3b (P = .008) genotypes were higher in patients than control subjects. No significant association was demonstrated between the HPA variants and 1-, 2- and 3-vessel disease. HPA-1b/2a/3b (Pc = .021) and HPA-1b/2b/3a (Pc = .002) haplotypes were positively associated with CAD, thereby conferring a disease susceptibility nature to these haplotypes. Multivariate analysis confirmed the positive association of HPA-1b/2a/3b (aOR = 3.72; 95% CI = 1.49-9.28), and in addition identified HPA-1b/2a/3a (aOR = 2.49; 95% CI = 1.06-5.86) to be positively associated with CAD, after adjusting for a number of covariates. Our results demonstrate positive association of HPA variants and specific HPA-1/HPA-2/HPA-3 haplotypes with CAD in Tunisians.
Subject(s)
Antigens, Human Platelet/genetics , Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Haplotypes , Polymorphism, Single-Stranded Conformational , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
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.
