Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications
| Autor: | Jane I. Grove, Robin M. Delahay, Kalaiyarasi Kaliyaperumal, Guruprasad P. Aithal, William J.H. Griffiths, Adam Duckworth |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine Drug Candidate gene media_common.quotation_subject Single-nucleotide polymorphism Human leukocyte antigen Bioinformatics 03 medical and health sciences 0302 clinical medicine Genetic predisposition Humans Medicine Allele media_common Genetic association Hepatology business.industry Alanine Transaminase Bilirubin Liver Transplantation 030104 developmental biology Liver Pharmacogenetics Pharmacogenomics Female 030211 gastroenterology & hepatology Chemical and Drug Induced Liver Injury business HLA-DRB1 Chains |
| Zdroj: | Journal of Hepatology. 69:948-957 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2018.05.013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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