A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibalpha.
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Matsubara Y, Murata M, Moriki T, Yokoyama K, Watanabe N, Nakajima H, Handa M, Kawano K, Aoki N, Yoshino H, Ikeda Y
A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibalpha.
Thromb Haemost. 2002 May;87(5):867-72.
- PubMed ID
- 12038791 [ View in PubMed]
- Abstract
Platelet glycoprotein (GP) Ib/IX/V complex mediates high-shear dependent platelet activation through an interaction with the von Willebrand factor (vWF). All four subunits of the complex have a structural motif, the leucine-rich repeat (LRR) sequence, with leucines in conserved positions. Here we report a new polymorphism, Leu/Phe at residue 70 of GPIbalpha, which disrupts the consensus sequence of the LRR in the vWF binding domain. Genotype frequencies among 142 healthy Japanese subjects were 92.3%, 7.7%, and 0.0%, for the 70Leu/Leu, 70Leu/Phe, and 75Phe/Phe genotypes, respectively. Ristocetin-induced or shear-induced platelet aggregation was not significantly different between the 70Leu/Leu and 70Leu/Phe genotypes. In in vitro studies, a recombinant GPIbalpha fragment with 70Phe (L70F) as compared to that with 70Leu (WT) had low reactivity to anti-GPIbalpha monoclonal antibodies, GUR20-5 and Hip1, both of which recognize conformation-specific epitopes within the 45-kDa domain. Ristocetin-induced 125I-vWF binding to L70F, however, did not differ from that to WT.