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Objectives: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention. Materials and Methods: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate. Results: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels. Conclusions: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment.

Background This study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms. Methods and Results We genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T‐allele carriers have a higher major adverse cardiac or cerebrovascular events risk post‐CABG than those who are CC homozygotes (hazard ratio [HR]=1.29; P =0.022). The clinical association between the risk allele (T) carriage and major adverse cardiac or cerebrovascular events was confirmed in another cohort study, which included 646 CABG patients from various health centers across China. Meanwhile, rs1126643 T allele was also linked with increased risk of major adverse cardiac or cerebrovascular events (HR=1.73; P =0.019). To explore the underlying mechanisms, we prospectively recruited 131 coronary artery disease patients, assessed their platelet aggregation function, and focused on detecting their GPIA mRNA level and protein expression. Results showed that patients with rs1126643 T allele have elevated platelet aggregation activity ( P =0.029) when protein expression is increased ( P Conclusions The synonymous common variant, GPIA rs1126643, increases the long‐term adverse events risk of CABG by augmenting GPIa protein expression and enhancing platelet aggregation function. This finding can serve as the implication of improving secondary prevention of CABG patients.

Response variability to antiplatelet treatment has been described and the widespread use of acetylsalicylic acid (ASA) and clopidogrel requires clarification of the residual platelet reactivity (RPR). Various glycoprotein Ia (GpIa) polymorphisms have been investigated, but their influence on platelet reactivity in myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI) on dual antiplatelet treatment is not still elucidated. Aim of this study was to evaluate the effect of C807T, G873A and T837C polymorphisms of GpIa on modulating platelet function in MI patients on dual antiplatelet treatment undergoing PCI. We measured platelet function by both a point-of-care assay (PFA100) and platelet-rich-plasma aggregation in 289 MI patients undergoing PCI and receiving dual antiplatelet treatment. Our data show that C807T/G873A polymorphisms, but not T837C, are associated with higher platelet reactivity. Carriers of the 807T/873A allele had significantly higher platelet aggregation values after arachidonic acid (AA) and collagen stimuli and, even if they did not reach the statistical significance, after 2 and 10μM ADP stimuli; 807T/873A allele carriers had also significantly shorter closure times on PFA100/epinephrine membranes. At the multiple analyses, C807T/G873A polymorphisms resulted an independent risk factor for RPR defined by both AA induced platelet aggregation (OR=3.0, 95%CI 1.17–7.89, p =0.022) or by PFA100/epinephrine (OR=4.1, 95%CI 1.53–10.89, p =0.005). In conclusion, this study shows the 807T/873A allele of the GpIa gene is an independent risk factor for the RPR on dual antiplatelet treatment, and extends, in a larger acute coronary syndrome population, the observation that the 807T/873A allele is associated with higher platelet reactivity.

Glycoprotein (GP) Ia/IIa plays a key role in platelet function by acting as a primary receptor for subendothelial collagen, thereby contributing to arterial thrombosis. In this study, we found that the expression level of platelet GPIa/IIa among Taiwan Chinese varies over sixfold and this difference relates either to the GPIa gene 807 C/T dimorphisms or the appearance of BglII restriction sequence within intron G. This is the first study to demonstrate the wide variation of platelet GPIa/IIa density in an Oriental population and its correlation to the GPIa gene polymorphisms. These results provide useful tools for predicting platelet GPIa/IIa density of Chinese. Keywords:: collagen, glycoprotein Ia/IIa density, glycoprotein Ia gene polymorphism

At sites of vascular injury, the platelet collagen receptor Glycoprotein Ia/IIa (GPIa/IIa) acts as an important mediator of platelet adhesion to fibrillar collagens. Two silent polymorphisms (807C/T and 873G/A) within the glycoprotein Ia gene have been implicated in increased risk of developing thrombosis and myocardial infarction in affected individuals. To provide basis for future studies, we examined the frequency of these GPIa polymorphisms for people in Turkey. We analyzed 118 unrelated individuals for their genotypes of the GPIa gene using a multiplexed allele specific-PCR based method. The allelic frequencies were found to be 34% for 807T/873A and 66% for 807C/873G; the genotypic frequencies were 13% for 807TT/873AA, 44% for 807CT/873GA, and 43% for 807CC/873GG. Am. J. Hematol. 69:83-84, 2002. © 2002 Wiley-Liss, Inc.

In recent years this laboratory has been concerned with defining a second class of I-region-associated (Ia) antigens in the mouse that are carbohydrate in nature and distinct from the conventional glycoprotein Ia antigens described by other laboratories (1). Based on these findings we have proposed that recognition of carbohydrate MHC antigens by MHC-controlled glycosyltransferases may be a mechanism of communication between lymphoid cells (2). In support of this proposal we recently reported (3,4) that certain monosaccharides can selectively inhibit in vitro secondary IgG responses to T-dependent antigens. Furthermore, although N-acetyl-D-galactosamine (GalNAc) inhibited the IgG response of all mouse strains tested, L-fucose (Fuc) only inhibited IgG production in the H-2 k haplotype, an effect that mapped to the I-J subregion (4). Similarly, D-galactose (Gal) and N-acetyl-D-mannosamine (ManNAc) inhibited IgG synthesis in b and d haplotypes and this inhibition was under I-C subregion control (4).