In:
Hepatology Research, Wiley, Vol. 53, No. 5 ( 2023-05), p. 440-449
Abstract:
Drug‐induced liver injury (DILI) is a severe and life‐threatening immune‐mediated adverse effect, occurring rarely among treated patients. We examined genomic biomarkers in the Japanese population that predict the onset of DILI after using a certain class of drugs, such as Kampo products (Japanese traditional medicines). Methods A total of 287 patients diagnosed as DILI by hepatology specialists were recruited after written informed consent was obtained. A genome‐wide association analysis and human leukocyte antigen (HLA) typing in four digits were performed. Results We found a significant association ( p = 9.41 × 10 −10 ) of rs146644517 ( G 〉 A ) with Kampo product–related DILI. As this polymorphism is located in the HLA region, we evaluated the association of HLA types and found that 12 (63.2%) of 19 Kampo‐DILI patients contained HLA‐B*35:01 , whereas only 15.2% were positive for this HLA among healthy volunteers. The odds ratio was 9.56 (95% confidence interval 3.75–24.46; p = 2.98 × 10 −6 , corrected p = 4.17 × 10 −5 ), and it increased to 13.55 compared with the DILI patients not exposed to Kampo products. The individual crude drug components in the Kampo products, including Scutellaria root ( ougon in Japanese), rhubarb ( daiou ), Gardenia fruit ( sanshishi ), and Glycyrrhiza ( kanzou ), were significantly associated with HLA‐B*35:01 . Conclusions HLA‐B*35:01 is a genetic risk factor and a potential predictive biomarker for Kampo‐induced DILI in the Japanese population.
Type of Medium:
Online Resource
ISSN:
1386-6346
,
1872-034X
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2006439-1
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