The GNB3 C825T polymorphism influences platelet aggregation in human whole blood

Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G-protein β-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation.

Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.2 years ±11.7 SD). Genotypes were determined using pyrosequencing and restriction analysis. Data were analyzed by linear one-way analysis of variance and Student's t-test, linear and multiple regression, and the χ(2)-test, as appropriate.

Homozygous carriers of the GNB3 825C-allele showed significantly (P≤0.022) increased maximum aggregation for EC(75) dosages compared with CT and TT genotypes [e.g. ADP: CC 150±36 vs. TT 126±33 aggregation unit (AU); thrombin receptor activating peptide: CC 175±46 vs. TT 150±38 AU; U46619: CC 164±33 vs. 149±32 AU; epinephrine: CC 66±41 vs. TT 48±34 AU]. In contrast, genotypes of glycoprotein IIb/IIIa PI(A)-polymorphism had no effect. Regression analysis revealed the GNB3 C825T polymorphism as an independent factor for enhanced platelet aggregation, besides factors such as female sex and blood cell values.

In human whole blood, the GNB3 825CC genotype is associated with enhanced platelet aggregation.