| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學碩士班/博士班 === 102 === G-protein mediated signal transduction is one of the important message delivery mechanisms in the cell. The intensity of the signal positively correlated to the reactivity of the cell. β subunit is the downstream signal from the dissociated Gi-protein and the 825T allele of the gene GNB3 encoding the G-protein β-3 subunit is predictive of enhanced signal transduction via Gi-proteins. Since the P2Y12 receptor on the surface of platelet is a Gi-coupled receptor mediating platelet activation by adenosine diphosphate (ADP), enhanced signal transduction in the 825T allele carrier would be associated with increased platelet aggregation by ADP. We tested this notion in Taiwanese population, in which 114 healthy adults (20-40 year-old), including 50 males and 64 females, were enrolled in this study.
The frequencies of the GNB3 C825T genotype in all subjects are in accord with the rule of Hardy-Weinberg principle. They are 15.2% for CC homozygous (n=18), 55.2% for CT heterozygous (n=63), and 29% for TT homozygous (n=33). We evaluated the platelet aggregating response to ADP (2.5-30 μM) with light transmittance aggregometry using adjusted platelet-rich plasma. Significant variation of ADP-induced platelet aggregation among individuals were shown to be associated with the GNB3 gene C825T polymorphism in the female group. Female subjects carrying the T allele (CT and TT) exhibited an enhanced platelet aggregating response to ADP (5 and 10 μM) (p<0.05). This individual variability of ADP-induced platelet aggregation became insignificant as the platelet had been pretreated with a cyclooxygenase inhibitor (Aspirin, 400 μg/ml) blocking thromboxane A2 formation, suggesting that enhanced platelet response to ADP for the 825T allele carriers could be attributed to the formation of more thromboxane A2 and/or enhanced action of thromboxane A2 following ADP stimulation.
This inter-individual difference in gene polymorphism may help us to adjust the antiplatelet therapy and reduce the risk of thromboembolism more effectively.
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