ArticleOmics : a journal of integrative biology2017
Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back-Looking Forward to Next-Generation Innovation.
Article in Omics : a journal of integrative biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- A blinded in vitro analysis of the intrinsic immunogenicity of hepatotoxic drugs: implications for preclinical risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Blood coagulation factors and platelet response to drug-induced hepatitis and hepatosis in rats.Animal models and experimental medicine · 2023Article
- Article
- Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases.Micromachines · 2021Review
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- Conference report: pharmacogenomics in special populations at WCP2018.British journal of clinical pharmacology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiosyncratic drug-induced hepatotoxicity is a formidable challenge for rational drug discovery and development, as well as the science of personalized medicine. There is evidence that hereditary factors, in part, contribute to drug toxicity. This expert analysis and review offer the insights gained, and the challenges ahead, for genome-wide association studies (GWASs) of idiosyncratic drug-induced hepatotoxicity. Published articles on genome-wide and subsequent replication studies were systematically searched in the PubMed electronic database. We found that the genetic risk variants that were identified genome-wide, and replication confirmed, are mainly related to polymorphisms in the human leukocyte antigen (HLA) region that include HLA-DQB1*06:02 for amoxicillin-clavulanate, HLA-B*57:01 for flucloxacillin, HLA-DRB1*15:01 for lumiracoxib, and HLA-DRB1*07:01 for lapatinib and ximelagatran-induced hepatotoxicity. Additionally, polymorphisms in ST6 β-galactosamide α-2, 6-sialyltranferase-1 (ST6GAL1), which plays a role in systemic inflammatory response, and variants in intron of family with sequence similarity-65 member-B (FAM65B) that play roles in liver inflammation displayed association with flucloxacillin and antituberculosis drug-induced hepatotoxicity, respectively. Taken together, these GWAS findings offer molecular leads on the central role that the immune system plays in idiosyncratic drug-induced hepatotoxicity. We conclude the expert review with a brief discussion of the salient challenges ahead. These include, for example, the need for discursive discovery paradigms that incorporate alternating GWASs and candidate gene studies, as well as the study of the environtome, the entire complement of environmental factors, including science and innovation policies that enact on global society and the human host, and by extension, on susceptibility for idiosyncratic drug-induced hepatotoxicity.
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