title: Platelet response to a small molecule inhibitor of α2β1 integrin is associated with ITGA2 C807T dimorphism.
abstract: High expression of the collagen receptor, α2β1 integrin, on platelets of ITGA2 807T-allele carriers has been identified as a risk factor for thromboembolic conditions, and α2β1 inhibitors are considered to be potential therapeutic agents. In 59 genotyped individuals, we measured α2 expression levels on platelets and analyzed platelet adhesion to collagen under flow conditions. A sulfonamide-type small-molecule inhibitor of α2β1 integrin decreased average platelet adhesion in individuals with the C/T807T genotype but not in those harboring C807C. Thus, genotype can be used to select a human subpopulation that has the highest probability of showing a positive response to α2β1 inhibitors.
authors.affiliation: a Department of Biochemistry , University of Turku , Turku , Finland.|b BioTie Therapies Corp ., Turku , Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Nissinen
authors.affiliation: a Department of Biochemistry , University of Turku , Turku , Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Rappu
authors.affiliation: b BioTie Therapies Corp ., Turku , Finland.
authors.forename: Pauli
authors.initials: P
authors.lastname: Ollikka
authors.affiliation: b BioTie Therapies Corp ., Turku , Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Nieminen
authors.affiliation: a Department of Biochemistry , University of Turku , Turku , Finland.|b BioTie Therapies Corp ., Turku , Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Marjamäki
authors.affiliation: a Department of Biochemistry , University of Turku , Turku , Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
mesh_terms: D000328:Adult; D000483:Alleles; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D055815:Young Adult
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D038982:Integrin alpha2beta1; D003094:Collagen; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone
keywords: Collagen receptor; inhibitor; integrin; platelets; polymorphism