Mutations of the Platelet Thromboxane A2 (TXA2) Receptor in Patients Characterized by the Absence of TXA2–induced Platelet Aggregation despite Normal TXA2 Binding Activity

Wataru Higuchi; Ichiro Fuse; Akira Hattori; Yoshifusa Aizawa

doi:10.1055/s-0037-1614866

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(05): 1528-1531
DOI: 10.1055/s-0037-1614866

Rapid Communications

Schattauer GmbH

Mutations of the Platelet Thromboxane A₂ (TXA₂) Receptor in Patients Characterized by the Absence of TXA₂–induced Platelet Aggregation despite Normal TXA₂ Binding Activity

Wataru Higuchi

¹From the First Department of Internal Medicine, Niigata University School of Medicine, Japan

,

Ichiro Fuse

¹From the First Department of Internal Medicine, Niigata University School of Medicine, Japan

,

Akira Hattori

²Internal Medicine, Sado Kouseiren Hospital, Japan

,

Yoshifusa Aizawa

¹From the First Department of Internal Medicine, Niigata University School of Medicine, Japan

› Author Affiliations

Abstract

Summary

Previously, we reported five cases of platelet dysfunction characterized by the absence of thromboxane A₂ (TXA₂) – induced platelet aggregation despite normal TXA₂ binding activity. In this platelet disorder, patients were divided into two groups; i.e. those whose platelets lacked or did not lack phospholipase C (PLC) activation (Group A and Group B, respectively) (Thromb Haemost 1996; 76: 1080). Furthermore, in one of the patients, we showed that a single amino acid substitution (Arg⁶⁰ to Leu) in the first cytoplasmic loop of the TXA₂ receptor (TXR) was responsible for this platelet disorder. However, mutational analysis of the TXR in the remaining patients has not been performed. Based on this background, we investigated the mutations of the TXR in these patients, and found that all of the patients have the same abnormality of the TXR (Arg⁶⁰ → Leu), although the Group A patients were homozygous and the Group B patients were heterozygous for this mutation.

This mutation is the only abnormality which has been found in this platelet disorder, and in patients heterozygous for this mutation, the mutant type TXR suppresses wild-type receptor-mediated platelet aggregation by a mechanism independent of PLC activation.

Keywords

Platelet dysfunction - thromboxane A₂ - receptor - point mutation

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References

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