Abstract
The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the Pl A2polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GPIIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and adenosine diphosphate (ADP) were determined. Allele frequencies of Pl A1 and Pl A2 were 0.84 and 0.16, respectively. The presence of one or two Pl A2 alleles was associated with increased platelet aggregability as indicated by incremen- tally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 µmol/L (0.9–1.0) for homozygous Pl A1, 0.7 µmol/L (0.7–0.9) for the heterozygous Pl A1/ Pl A2 and 0.6 µmol/L (0.4–1.0) for homozygous Pl A2 individuals, p = 0.009. The increase in aggregability induced by epinephrine remained highly significant (p = 0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 µmol/L (3.0–3.2), 3.0 µmol/L (2.9–3.2), and 2.8 µmol/L (2.4–3.3), p = 0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GPIIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the Pl A2 allotype with increased risk for cardiovascular disease.
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Feng, D. et al. (2000). Increased platelet aggregability associated with platelet GPIIIa PIA2 polymorphism: the Framingham Offspring Study. In: Zehender, M., Just, H., Breithardt, G. (eds) From Molecule to Men. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-57724-6_16
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DOI: https://doi.org/10.1007/978-3-642-57724-6_16
Publisher Name: Steinkopff, Heidelberg
Print ISBN: 978-3-642-63338-6
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