title: Identification of ADRA2A polymorphisms related to shear-mediated platelet function.
abstract: alpha2A 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, 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.
authors.affiliation: The Keio-Daiichi Project on Genetics of Thrombosis, Keio University, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yabe
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishihara
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shibano
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Omae
authors.forename: Gentaro
authors.initials: G
authors.lastname: Watanabe
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D044466:Asian People; D001483:Base Sequence; D001792:Blood Platelets / Q000502:physiology*; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007564:Japan; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011110:Polymorphism, Genetic / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000502:physiology; D033081:Shear Strength
chemical_list: C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2; D004837:Epinephrine