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

• Published in: Cardiovascular pathology Vol. 19; no. 5; pp. 302 - 307
• Main Authors: Abboud, Nesrine, Amin, Haitham, Ghazouani, Lakdhar, Khalifa, Sonia Ben Haj, Khalafallah, Ali Ben, Aded, Fawzi, Almawi, Wassim Y, Mahjoub, Touhami
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2010
• Subjects: Antigens, Human Platelet - genetics; Blood Platelets; Coronary artery disease; Coronary Artery Disease - genetics; Female; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Haplotypes; Human platelet alloantigens; Humans; Isoantigens; Male; Middle Aged; Pathology; PCR; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Factors; Tunisia; Tunisia; Gene polymorphism; Coronary artery disease; Human platelet alloantigens; PCR
• ISSN: 1054-8807; 1879-1336
• DOI: 10.1016/j.carpath.2009.04.003

Abstract 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.