alpha 2A adrenergic receptor (ADRA2A) on platelets interacts with epinephrine, which has a key role in regulating platelet functions. There is familial clustering of inter-individual variations in the epinephrine-induced platelet aggregation, the molecular basis of which, however, has not been fully understood. In this study, we screened the sequence variations in the transcriptional region of ADRA2A gene and analyzed the relationship between the two common polymorphisms and platelet function using epinephrine/collagen cartridge in the platelet function analyzer-100 system (R), in a healthy Japanese male population (n = 211). Among the identified 16 sequence variations including five novel variations, 1780GG genotype was associated with longer closure time which represents low platelet function under high shear-stress conditions (p = 0.0478). We also observed enhanced effect of the combination of 1780GG and 2372AA genotypes on longer closure time (p = 0.0319). These findings suggest that 1780A/G and 2372A/G polymorphisms are associated with platelet function in interactions with collagen/epinephrine. (c) 2006 Elsevier Inc. All rights reserved.