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Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis?
PURPOSE OF REVIEW: The pathogenesis of DILI is currently unknown; however, research has shown strong genetic associations with some DILIs. This paper describes the variant alleles uncovered by GWAS and discusses their potential role as susceptibility biomarkers. RECENT FINDINGS: An association with...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556130/ https://www.ncbi.nlm.nih.gov/pubmed/28856081 http://dx.doi.org/10.1007/s11901-017-0363-9 |
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author | Clare, Kathleen E. Miller, Michael H. Dillon, John F. |
author_facet | Clare, Kathleen E. Miller, Michael H. Dillon, John F. |
author_sort | Clare, Kathleen E. |
collection | PubMed |
description | PURPOSE OF REVIEW: The pathogenesis of DILI is currently unknown; however, research has shown strong genetic associations with some DILIs. This paper describes the variant alleles uncovered by GWAS and discusses their potential role as susceptibility biomarkers. RECENT FINDINGS: An association with HLADRB1*15:01 and amoxicillin/clavulanate DILI has been shown by a number of research groups. The presence of the HLA-B*57:01 allele has been associated with an 81-fold increased risk of flucloxacillin DILI. The HLA-B*35:02 allele has significant association with minocycline DILI. SUMMARY: With the exception of abacavir for HIV therapy, no other prospective genetic screening tests have met the threshold for clinical application. This is largely because DILI incidence is too low to warrant the cost and effort associated with testing. Perhaps, with the development of personalised medicine, a panel of genes for disease susceptibility, drug efficacy and adverse reactions could be tested once off. This would change the cost-effectiveness paradigm, personalise healthcare and reduce DILI risk by avoiding medications in patients with specific HLA alleles. |
format | Online Article Text |
id | pubmed-5556130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-55561302017-08-28 Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? Clare, Kathleen E. Miller, Michael H. Dillon, John F. Curr Hepatol Rep Drug-Induced Liver Injury (F Bessone and R Andrade, Section Editors) PURPOSE OF REVIEW: The pathogenesis of DILI is currently unknown; however, research has shown strong genetic associations with some DILIs. This paper describes the variant alleles uncovered by GWAS and discusses their potential role as susceptibility biomarkers. RECENT FINDINGS: An association with HLADRB1*15:01 and amoxicillin/clavulanate DILI has been shown by a number of research groups. The presence of the HLA-B*57:01 allele has been associated with an 81-fold increased risk of flucloxacillin DILI. The HLA-B*35:02 allele has significant association with minocycline DILI. SUMMARY: With the exception of abacavir for HIV therapy, no other prospective genetic screening tests have met the threshold for clinical application. This is largely because DILI incidence is too low to warrant the cost and effort associated with testing. Perhaps, with the development of personalised medicine, a panel of genes for disease susceptibility, drug efficacy and adverse reactions could be tested once off. This would change the cost-effectiveness paradigm, personalise healthcare and reduce DILI risk by avoiding medications in patients with specific HLA alleles. Springer US 2017-08-07 2017 /pmc/articles/PMC5556130/ /pubmed/28856081 http://dx.doi.org/10.1007/s11901-017-0363-9 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Drug-Induced Liver Injury (F Bessone and R Andrade, Section Editors) Clare, Kathleen E. Miller, Michael H. Dillon, John F. Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title | Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title_full | Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title_fullStr | Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title_full_unstemmed | Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title_short | Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? |
title_sort | genetic factors influencing drug-induced liver injury: do they have a role in prevention and diagnosis? |
topic | Drug-Induced Liver Injury (F Bessone and R Andrade, Section Editors) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556130/ https://www.ncbi.nlm.nih.gov/pubmed/28856081 http://dx.doi.org/10.1007/s11901-017-0363-9 |
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