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Thromb Haemost 2002; 87(05): 867-872
DOI: 10.1055/s-0037-1613098
Review Article
Schattauer GmbH

A Novel Polymorphism, 70Leu/Phe, Disrupts a Consensus Leu Residue within the Leucine-rich Repeat Sequence of Platelet Glycoprotein Ibα

Yumiko Matsubara
4   Department of Medicine, School of Medicine, Keio University, Tokyo
,
Mitsuru Murata
4   Department of Medicine, School of Medicine, Keio University, Tokyo
,
Takanori Moriki
1   Health Center, Keio University, Tokyo, Japan
,
Kenji Yokoyama
4   Department of Medicine, School of Medicine, Keio University, Tokyo
,
Naohide Watanabe
4   Department of Medicine, School of Medicine, Keio University, Tokyo
,
Hideaki Nakajima
2   Blood Center, School of Medicine, Keio University, Tokyo, Japan
,
Makoto Handa
2   Blood Center, School of Medicine, Keio University, Tokyo, Japan
,
Koichi Kawano
3   Second Department of Internal Medicine, Kyorin University, Tokyo, Japan
,
Nobuo Aoki
3   Second Department of Internal Medicine, Kyorin University, Tokyo, Japan
,
Hideaki Yoshino
3   Second Department of Internal Medicine, Kyorin University, Tokyo, Japan
,
Yasuo Ikeda
4   Department of Medicine, School of Medicine, Keio University, Tokyo
› Author Affiliations
Further Information

Publication History

Received 22 October 2001

Accepted after revision 24 January 2002

Publication Date:
11 December 2017 (online)

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Summary

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 GPIbα, 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 70Phe/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 GPIbα fragment with 70Phe (L70F) as compared to that with 70Leu (WT) had low reactivity to anti-GPIbα monoclonal antibodies, GUR20-5 and Hip1, both of which recognize conformation-specific epitopes within the 45-kDa domain. Ristocetininduced 125I-vWF binding to L70F, however, did not differ from that to WT.

Keywords

Polymorphism - platelets - glycoprotein Iba - leucine-rich repeat - genetics
 

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