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Association of HLA-DRB1*04:05 allele with drug-induced interstitial lung disease in Japanese population

The Pharmacogenomics Journal volume 20, pages 823–830 (2020)Cite this article

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Abstract

Drug-induced interstitial lung disease (DILD) is a life-threatening adverse reaction. The Japanese population is more susceptible to DILD as compared with other populations, suggesting its pathogenesis could vary depending on ethnic genetic background. We conducted case-control studies to elucidate the association between DILD and HLA alleles in the Japanese. The 177 clinically diagnosed DILD patients and 3002 healthy controls for exploration and 55 DILD patients and 201 healthy controls for validation were genotyped for four HLA genes. HLA-DRB1*04:05 was significantly associated with DILD (corrected p = 0.014); this was also validated in the other set of patients/controls. Chemical drugs other than protein therapeutics showed this association (p = 1.7 × 10−4) . The Japanese population showed a higher HLA-DRB1*04:05 frequency than most other populations. In conclusion, HLA-DRB1*04:05 could be associated with DILD susceptibility in Japanese individuals, and its high general frequency may explain the high reported incidence of DILD in Japanese.

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Fig. 1: Comparison of HLA-DRB1*04:05 carrier frequency among different countries worldwide.

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Acknowledgements

This study was supported by AMED under Grant Number 18mk0101085j0002. We are sincerely indebted to all participants of this study. We thank Ms. Mika Suzuki for her invaluable help in carrying out this study.

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Author notes

  1. These authors contributed equally: Takuya Imatoh, Atsuhito Ushiki, Masao Ota

Authors and Affiliations

  1. Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan

    Takuya Imatoh, Ryosuke Nakamura, Kosuke Saito & Yoshiro Saito

  2. The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan

    Atsuhito Ushiki, Michiko Ito & Masayuki Hanaoka

  3. Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan

    Masao Ota

  4. Center for Preventive Medical Science, Chiba University, Chiba, Japan

    Akihiro Sekine, Taiki Yamashita & Yoichi Mashimo

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  1. Takuya Imatoh
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Correspondence to Yoshiro Saito or Masayuki Hanaoka.

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Imatoh, T., Ushiki, A., Ota, M. et al. Association of HLA-DRB1*04:05 allele with drug-induced interstitial lung disease in Japanese population. Pharmacogenomics J 20, 823–830 (2020). https://doi.org/10.1038/s41397-020-0172-3

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