HPA-1 and HPA-3 Polymorphisms of the Platelet Fibrinogen Receptor and Coronary Artery Disease and Myocardial Infarction

Abstract

SummaryPlatelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa) plays a fundamental role in atherothrombosis. The human platelet antigen (HPA) -1 and the HPA-3 are the most extensively studied polymorphisms of GPIIIa and GPIIb, respectively. This study was designed to test, in a large population, the hypothesis that these polymorphisms represent a risk factor for the occurrence of coronary artery disease (CAD) and myocardial infarction (MI).Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (CAD, n = 998) and those with old or acute MI constituted the group with MI (MI, n = 793). As controls served subjects, matched with patients for age and sex, with neither angiographic CAD nor symptoms or signs of MI (matched controls [MC], n = 340) as well as a group of blood donors without cardiac symptoms or signs of CAD (BD, n = 104). Genotype distribution was similar across the groups; HPA-1a/a: HPA-1a/b: HPA-1b/b was 75.0%: 22.1%: 2.9% in BD, 72.6%: 24.7%: 2.6% in MC, 70.5%: 26.8%: 2.7% in CAD, and 70.7%: 26.4%: 2.9% in MI; HPA-3a/a: HPA-3a/b: HPA-3b/b was 39.4%: 40.4%: 20.2% in BD, 33.5%: 50.0%: 16.5% in MC, 35.0%: 46.4%: 17.0% in CAD, and 37.1%: 48.0%: 16.5% in MI. There was no interaction between these polymorphisms, nor between each of these polymorphisms and other risk factors.Thus, the HPA-1 and HPA-3 polymorphisms are neither separately nor in concert associated with any measurable increase of the risk for CAD or MI in angiographically evaluated subjects.

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

“…Since the initial report of Weiss linking HPA-1b allele with myocardial infarction among young patients [19], a number of clinical studies demonstrated an association between HPA polymorphic variants and platelet hyperaggregation accompanying acute coronary syndromes [20][21][22], but with inconsistent findings [23][24][25]. These discrepancies may be explained by differences in selection of study subjects and study design, since the impact of single genetic factors on the risk of CAD may be higher when examined along with other additional inherited or acquired risk factors.…”

Platelet Glycoprotein IIb HPA-3 a/b Polymorphism Is Associated with Native Arteriovenous Fistula Thrombosis in Chronic Hemodialysis Patients

“…The studies to determine whether the HPA-3 a/b polymorphism might be associated with increased thrombotic risk are less, and some studies found that HPA-3b was associated with a higher thrombotic risk, 15,16 whereas others did not. 17,18 The association between ESRD as well as native AVF thrombosis and the HPA-3 a/b polymorphism has not been studied in the Chinese population. In this study, we examined the association of the HPA-3 a/b polymorphism in Chinese Han patients suffering from ESRD.…”

The Genetics of Thrombosis

“…Hence, it appears that the Pro33 polymorphism of glycoprotein IIIa alters human platelet aggregation, adhesion, and secretion, perhaps through the mechanism of increased signaling and cytoskeletal changes, leading to stabilization of platelet-platelet and/or platelet-extracellular matrix interactions (236). Another variant that has been studied in the GPIIb-IIIa gene is the Ile843Ser polymorphism that has been shown to be associated with increased risk of MI in young women in the presence of other risk factors (247), but other studies have shown negative results (248,249).…”