title: Alpha 2A adrenergic receptor polymorphism is associated with plasma von Willebrand factor levels in a general population.
abstract: High levels of plasma von Willebrand factor are a proposed risk factor for atherothrombotic disorders. Previously, ABO blood type and the von Willebrand factor -1793C/G polymorphism were shown to affect interindividual variations in plasma von Willebrand factor levels. We previously reported that polymorphisms of the alpha 2A adrenergic receptor, an epinephrine receptor, were associated with platelet function as assessed by platelet function analyzer-100. The measurement value of platelet function analyzer-100 has been reportedly associated with plasma von Willebrand factor levels. Also, it was demonstrated that epinephrine administration increases plasma von Willebrand factor levels in vivo. Thus, the present study investigated the association between plasma von Willebrand factor levels and genetic polymorphisms as follows: ABO blood type, von Willebrand factor -1051G/A (linked with -1793C/G), alpha 2A adrenergic receptor 1780A/G, and alpha 2A adrenergic receptor 2372A/G. Study subjects were genetically unrelated Japanese men (n = 277) recruited at their regular medical examinations. Genotyping of the polymorphisms was performed using the single nucleotide primer extension-based method. Plasma von Willebrand factor levels were measured as ristocetin-cofactor activities. The O blood type and alpha 2A adrenergic receptor 2372AA genotype were significantly associated with lower von Willebrand factor levels, though von Willebrand factor -1051G/A polymorphism did not affect them. In stratification analysis of the group according to blood type O and non-O, the significant association between the 2372AA genotype and lower plasma von Willebrand factor levels was observed in non-O subjects, but not O subjects. In conclusion, the alpha 2A adrenergic receptor 2372A/G polymorphism is associated with plasma von Willebrand factor levels in a general population.
authors.affiliation: The Keio-Daiichi Sankyo 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: 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: D000017:ABO Blood-Group System / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D044466:Asian People; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D000017:ABO Blood-Group System; C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2; D014841:von Willebrand Factor