A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibα

Yumiko Matsubara, Mitsuru Murata, Takanori Moriki, Kenji Yokoyama, Naohide Watanabe, Hideaki Nakajima, Makoto Handa, Koichi Kawano, Nobuo Aoki, Hideaki Yoshino, Yasuo Ikeda

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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. Ristocetin-induced 125I-vWF binding to L70F, however, did not differ from that to WT.

Original languageEnglish
Pages (from-to)867-872
Number of pages6
JournalThrombosis and Haemostasis
Volume87
Issue number5
Publication statusPublished - 2002

Fingerprint

Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
von Willebrand Factor
Leucine
Ristocetin
Genotype
Platelet Activation
Consensus Sequence
Platelet Aggregation
Epitopes
Healthy Volunteers
Monoclonal Antibodies

Keywords

  • Genetics
  • Glycoprotein Ibα
  • Leucine-rich repeat
  • Platelets
  • Polymorphism

ASJC Scopus subject areas

  • Hematology

Cite this

A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibα. / Matsubara, Yumiko; Murata, Mitsuru; Moriki, Takanori; Yokoyama, Kenji; Watanabe, Naohide; Nakajima, Hideaki; Handa, Makoto; Kawano, Koichi; Aoki, Nobuo; Yoshino, Hideaki; Ikeda, Yasuo.

In: Thrombosis and Haemostasis, Vol. 87, No. 5, 2002, p. 867-872.

Research output: Contribution to journalArticle

Matsubara, Y, Murata, M, Moriki, T, Yokoyama, K, Watanabe, N, Nakajima, H, Handa, M, Kawano, K, Aoki, N, Yoshino, H & Ikeda, Y 2002, 'A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibα', Thrombosis and Haemostasis, vol. 87, no. 5, pp. 867-872.
Matsubara, Yumiko ; Murata, Mitsuru ; Moriki, Takanori ; Yokoyama, Kenji ; Watanabe, Naohide ; Nakajima, Hideaki ; Handa, Makoto ; Kawano, Koichi ; Aoki, Nobuo ; Yoshino, Hideaki ; Ikeda, Yasuo. / A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibα. In: Thrombosis and Haemostasis. 2002 ; Vol. 87, No. 5. pp. 867-872.
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AU - Moriki, Takanori

AU - Yokoyama, Kenji

AU - Watanabe, Naohide

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AU - Handa, Makoto

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AB - 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. Ristocetin-induced 125I-vWF binding to L70F, however, did not differ from that to WT.

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