Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications
A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidat...
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| Format: | Article |
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Elsevier
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51566/ |
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| author | Kaliyaperumal, Kalaiyarasi Grove, Jane I. Delahay, Robin M. Griffiths, William. J.H. Duckworth, Adam Aithal, Guruprasad P. |
| author_facet | Kaliyaperumal, Kalaiyarasi Grove, Jane I. Delahay, Robin M. Griffiths, William. J.H. Duckworth, Adam Aithal, Guruprasad P. |
| author_sort | Kaliyaperumal, Kalaiyarasi |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual’s susceptibility to DILI. On the other hand, a series of genome-wide association studies (GWASs) have revealed a number of Human Leucocyte Antigen (HLA) alleles that are associated with DILI secondary to compounds with dissimilar chemical structures, highlighting the role of adaptive immune responses in the development of liver damage. These risk alleles, such as HLA-DRB1*15:02 illustrated by the example presented in the clinical vignette, determine the physicochemical properties of the peptide-binding grooves of the HLA molecules and increase the likelihood of DILI in a susceptible individual by altering the nature or the magnitude of immune-mediated liver injury. Associations of HLA alleles with DILI secondary to specific drugs can be translated into genetic tests, and when performed selectively, can improve the accuracy of diagnosis of DILI as well as assist in identifying the correct causal agent when the event could be attributed to more than one drug. |
| first_indexed | 2025-11-14T20:21:09Z |
| format | Article |
| id | nottingham-51566 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:21:09Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-515662020-05-04T19:37:12Z https://eprints.nottingham.ac.uk/51566/ Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications Kaliyaperumal, Kalaiyarasi Grove, Jane I. Delahay, Robin M. Griffiths, William. J.H. Duckworth, Adam Aithal, Guruprasad P. A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual’s susceptibility to DILI. On the other hand, a series of genome-wide association studies (GWASs) have revealed a number of Human Leucocyte Antigen (HLA) alleles that are associated with DILI secondary to compounds with dissimilar chemical structures, highlighting the role of adaptive immune responses in the development of liver damage. These risk alleles, such as HLA-DRB1*15:02 illustrated by the example presented in the clinical vignette, determine the physicochemical properties of the peptide-binding grooves of the HLA molecules and increase the likelihood of DILI in a susceptible individual by altering the nature or the magnitude of immune-mediated liver injury. Associations of HLA alleles with DILI secondary to specific drugs can be translated into genetic tests, and when performed selectively, can improve the accuracy of diagnosis of DILI as well as assist in identifying the correct causal agent when the event could be attributed to more than one drug. Elsevier 2018-05-21 Article PeerReviewed Kaliyaperumal, Kalaiyarasi, Grove, Jane I., Delahay, Robin M., Griffiths, William. J.H., Duckworth, Adam and Aithal, Guruprasad P. (2018) Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications. Journal of Hepatology . ISSN 1600-0641 Drug-induced liver injury (DILI); Amoxicillin-clavulanic acid; HLA-DRB1*15:02; Major Histocompatibility Complex (MHC); Peptide-binding groove; diagnostic; genotyping https://www.sciencedirect.com/science/article/pii/S0168827818320592 doi:10.1016/j.jhep.2018.05.013 doi:10.1016/j.jhep.2018.05.013 |
| spellingShingle | Drug-induced liver injury (DILI); Amoxicillin-clavulanic acid; HLA-DRB1*15:02; Major Histocompatibility Complex (MHC); Peptide-binding groove; diagnostic; genotyping Kaliyaperumal, Kalaiyarasi Grove, Jane I. Delahay, Robin M. Griffiths, William. J.H. Duckworth, Adam Aithal, Guruprasad P. Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title | Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title_full | Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title_fullStr | Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title_full_unstemmed | Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title_short | Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications |
| title_sort | pharmacogenomics of drug-induced liver injury (dili): molecular biology to clinical applications |
| topic | Drug-induced liver injury (DILI); Amoxicillin-clavulanic acid; HLA-DRB1*15:02; Major Histocompatibility Complex (MHC); Peptide-binding groove; diagnostic; genotyping |
| url | https://eprints.nottingham.ac.uk/51566/ https://eprints.nottingham.ac.uk/51566/ https://eprints.nottingham.ac.uk/51566/ |