Platelet GP IIIa Pl ^A Polymorphisms Display Different Sensitivities to Agonists

Abstract

Pl(A2)-positive platelets displayed a lower threshold for activation, and platelets heterozygous for Pl(A) alleles showed increased sensitivity to 2 antiplatelet drugs. These in vitro platelet studies may have relevance for in vivo thrombotic conditions.

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

“…Clearly, PIA2-carriers generate more thrombin after microvascular trauma which underlines the functional meaning of this particular platelet SNP also suggesting some pharmagenomic importance [25,26]. A more complex interpretation can be derived from the data from another study showing that ligation of the PIA2-genotype integrin could affect outside-in signalling efficacy with the consequence of more intense platelet-platelet interaction, but also increased adherence to immobilized adhesion molecules.…”

Enhanced Activation of Mitogen-activated Protein Kinase and Myosin Light Chain Kinase by the Pro33 Polymorphism of Integrin β3

“…Integrin ␤ 3 is polymorphic at residue 33 (Leu 33 or Pro 33 ; also known as Pl A1 or Pl A2 , respectively), and the Pro 33 form has been associated with an enhanced adhesive phenotype in cell lines and platelets (12,13) and with acute coronary syndromes in some studies (14). This polymorphism is not rare, and 25% of individuals of Northern European descent express Pro 33 isoforms on their platelets.…”

“…Washed platelets were prepared as described (13), suspended in Tyrode's buffer, and allowed to recover for 2 h at 37°C. Fibrinogen (12.5 g/ml) or heat-denatured BSA was immobilized on six-well plates as described above.…”

“…Platelet Secretion Studies-Secretion of ␣-granules was studied by assaying for P-selectin expression using a modification of our previously described whole blood flow cytometric assay (13). Briefly, 10 l of washed platelets (2 ϫ 10 6 ) of known Pl A genotype were incubated with 10 l of 0.2 mg/ml fluorescein isothiocyanate-labeled anti-P-selectin antibody in a total of 40 l of Tyrode's buffer containing 10 mM HEPES and activated using varying concentrations of thrombin for 2 min.…”

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients

“…The HPA-1 minor allele is known to lower the threshold for platelet activation, alpha-granule release, and fibrinogen binding while increasing platelet sensitivity to antiplatelet drugs. [18,19]. The impact of missing a true effect of the minor allele for HPA-1 is overlooking a potential medical intervention.…”