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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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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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 (2020). https://doi.org/10.1038/s41397-020-0172-3