Human platelet alloantigens HPA-1, HPA-2, and HPA-3 polymorphisms associated with extent of severe coronary artery disease

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.

Association of human platelet alloantigens encoding gene polymorphisms with the risk of Coronary artery disease in Iranian patients

“…Our study is also consistent with a recent Tunisian study that reported the association of haplotypes containing HPA-1b allele, such as 1b/2a/3a and 1b/2a/3b with CAD risk. This association was still significant when it was adjusted for the traditional risk factors involved in the CAD development [19]. Our findings are in line with the results of prior research performed by Floyd et al in the UK.…”

“…It appeared that the relative effect of this polymorphism is decreased considerably with increasing in age and the presence of risk factors, such as blood pressure, diabetes, and cholesterol [20]. Nevertheless, our results are in apparent disagreement with previous reports indicating a positive association of HPA-1b and HPA-3b alleles with the risk of CAD in Tunisian patients [19], platelet hyper-reactivity in ACS [21,22], and increased thrombotic complications [8,23,24].…”

“…For instance, HPA-1b prevalence has been reported to be higher in Iranian healthy individuals (11%) than African (8%) [37], and Southeast Asians (1%) [38]. On the contrary, prevalence was lower than for Northern Europe (14-19%) [39,40], American populations (19.1%) [24], and Tunisians (45.4%), which is the utmost prevalence identified to date for all studied population ever [19].…”

Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage

“…To mimic exposure to β3 or GPIbα during conception, Itgb3 -/-and Gp1ba -/-both active and passive (postnatal antisera injections) murine models of FNAIT. As GPIbα is not constitutively expressed on ECs and anti-GPIbα antibody (i.e., anti-HPA-2a) is involved in FNAIT (36, 37), we used our anti-GPIbα-mediated FNAIT model as a control (37)(38)(39). Our findings demonstrate that antiplatelet β3, but not anti-GPIbα antibodies, impaired angiogenic signaling, inhibited angiogenesis, and induced ICH in the brain of murine fetuses and neonates, and this could be prevented by administration of intravenous immunoglobulin (IVIG) to the mother.…”

Correlation between polymorphism of platelet alloantigen genes HPA-1-5 and type 2 diabetes complication by carotid atherosclerosis in a Chinese population

“…Highly polymorphic distribution of HPA-2 among populations is one of the main factors affecting platelet function. Abboud et al (2010) found that the HPA-2 gene is not only an independent risk factor for coronary heart disease, but also correlates significantly with its severity. Nevertheless, Nomura et al (2006) found no significant difference in HPA-2 between T2DM patients, with or without atherosclerosis, and healthy people.…”