Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan.
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Pharmacogenomics J. 2020 Dec;20(6):823-830. doi: 10.1038/s41397-020-0172-3. Epub 2020 May 28.
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-DRB104:05 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) . The Japanese population showed a higher HLA-DRB104:05 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.
药物性间质性肺病（DILD）是一种危及生命的不良反应。与其他人群相比，日本人群更容易发生 DILD，这表明其发病机制可能因种族遗传背景而异。我们进行了病例对照研究，以阐明日本人群中 DILD 与 HLA 等位基因之间的关联。对 177 名临床诊断的 DILD 患者和 3002 名健康对照者进行了探索性基因分型，对 55 名 DILD 患者和 201 名健康对照者进行了验证，对四个 HLA 基因进行了基因分型。HLA-DRB104:05 与 DILD 显著相关（校正后 p=0.014）；在另一组患者/对照者中也得到了验证。除蛋白治疗药物外的化学药物也显示出这种关联（p=1.7×10）。日本人群 HLA-DRB104:05 的频率高于大多数其他人群。总之，HLA-DRB1*04:05 可能与日本个体的 DILD 易感性相关，其较高的普遍频率可能解释了日本报道的 DILD 发病率较高的原因。
