title: Genetic polymorphism in human platelet glycoprotein GP Ib/IX/V complex is enriched in GP V (CD42d).
abstract: Platelet glycoproteins Ib beta (CD42c), IX (CD42a), and V (CD42d), together with GP Ib alpha (CD42b), form a receptor whose interaction with the von Willebrand factor is essential in the initial stages of haemostasis. Genetic variation in these proteins can cause alloimmunization leading to neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness. Defective mutations cause a rare bleeding disorder, Bernard-Soulier syndrome. Only two antigenic polymorphisms have thus far been established in these proteins: the HPA-2 in GP Ib alpha and the rare Iy variant in GP Ib beta. Recently, we reported that only a limited degree of polymorphism can be found in the GP Ib alpha gene; the level of variation in the other components is not known. We therefore systematically screened polymorphism in the GP Ib beta, GP IX, and GP V genes in 50 unrelated Finnish blood donors. Nine polymorphic sites were found in the GP V gene, of which four changed the amino acid code and five were silent. The gene frequencies for substitutions Asp114Tyr, Met273Ile, Gly341Arg, and Leu397Arg were 1%, 1%, 2%, and 1% respectively. The five silent polymorphisms also had low frequencies, 1-4%. No polymorphism was found in the GP Ib beta gene and only one mutation was found in the 3' untranslated region of the GP IX gene. Our results indicate that genetic variation in the GP Ib/IX/V complex is mostly tolerated in the GP V protein--whose function in the complex is not clear whereas the other components have only very limited genetic polymorphism.
authors.affiliation: Finnish Red Cross Blood Transfusion Service, Helsinki.
authors.forename: S
authors.initials: S
authors.lastname: Koskela
authors.forename: R
authors.initials: R
authors.lastname: Kekomäki
authors.forename: J
authors.initials: J
authors.lastname: Partanen
mesh_terms: D001782:Blood Donors / Q000145:classification; D004247:DNA / Q000097:blood; D005387:Finland / Q000453:epidemiology; D005784:Gene Amplification / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D004247:DNA