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Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

The Pharmacogenomics Journal volume 7, pages 395–403 (2007)Cite this article

Abstract

Aspirin prevents the production of thromboxane A2 (TXA2) by irreversibly inhibiting platelet cyclooxygenase, exhibiting antiplatelet actions. This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infarction via this action mechanism. However, there are individual differences in this action, and aspirin is not effective in some patients, which is referred to as ‘aspirin resistance’. In this study, we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms (SNPs) of nine genes involved in platelet aggregation/hemorrhage. Among SNPs involved in platelet aggregation, aspirin was less effective for 924T homozygote of a TXA2 receptor, 924T>C, and 1018C homozygote of a platelet membrane glycoprotein GPIbα, 1018C>T, suggesting that 924T and 1018C alleles are involved in aspirin resistance.

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Acknowledgements

We thank Professor Masatsugu Hori, Graduate School of Medicine, Osaka University, Dr Masayoshi Murakami, Director, Foundation for Biomedical Research and Innovation, Dr Mitsuyoshi Nakashima, Professor Emeritus of Hamamatsu University School at Medicine, and Professor Junichi Azuma, Graduate School of Pharmaceutical Sciences, Osaka University for their advice and support. We also thank Ms Sayaka Nishio and Ms Hitomi Mukuta, JCL Bioassay Corporation for their support in the measurement of the blood levels of aspirin and salicylic acid, and Ms Haruka Uesaka-Isobe, a senior scientist of MediBIC Co. Ltd., for her support in genetic statistics.

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Authors and Affiliations

  1. Otsuka Pharmaceutical Co., Ltd., Osaka, Japan

    T Fujiwara, H Hishigaki & K Imagawa

  2. Takeda Pharmaceutical Company, Osaka, Japan

    M Ikeda & N Miyajima

  3. Astellas Pharma Inc., Tokyo, Japan

    K Esumi & Y Hashimoto

  4. Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan

    T D Fujita, T Hatoyama, T Asai, T Katsumata & T Yamamoto

  5. Tanabe Seiyaku Co., Ltd., Osaka, Japan

    M Kono, M Suzuki & S Horimoto

  6. Senju Pharmaceutical Co., Ltd., Osaka, Japan

    H Tokushige & T Ogawa

  7. Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Japan

    T Maeda & E Suzuki

  8. Shionogi & Co., Ltd., Osaka, Japan

    S Sasaki & T Sugawara

  9. Takara Bio Inc., Otsu, Japan

    F Hino & M Shimada

  10. Hitachi, Ltd., Kawagoe, Japan

    T K Fujita, H Zaima & Y Tsuzuki

  11. Maruyama Hospital, Hamamatsu, Japan

    S Sesoko

  12. Osaka University, Suita, Japan

    Y Fujisawa

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  1. T Fujiwara
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  2. M Ikeda
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  16. T K Fujita
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  19. T Sugawara
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  22. H Hishigaki
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  23. S Horimoto
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  26. K Imagawa
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Corresponding author

Correspondence to T Fujiwara.

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None declared.

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Fujiwara, T., Ikeda, M., Esumi, K. et al. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity. Pharmacogenomics J 7, 395–403 (2007). https://doi.org/10.1038/sj.tpj.6500435

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  • DOI: https://doi.org/10.1038/sj.tpj.6500435

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