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Drug-induced liver injury: past, present and future

Lookup NU author(s): Professor Ann Daly

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Abstract

Drug-induced liver injury (DILI) is a rare but potentially serious idiosyncratic reaction. By using candidate gene and genome-wide association studies, replicated associations for DILI susceptibility with HLA genes and genes relevant to drug metabolism have been detected, mainly since 2000. The HLA associations include a strong association between flucloxacillin-induced injury and the class I allele B*5701 and weaker associations for co-amoxiclav and ximelagatran DILI with the class II genotype. These associations suggest an injury mechanism involving an immune response, possibly to a complex of drug or metabolite and protein. For genes relevant to drug metabolism, the best replicated association is between isoniazid DILI and NAT2 slow acetylation. Homozygosity for GSTM1 null and/or GSTT1 null alleles also seems to be a risk factor for DILI, with associations described independently for several drugs. Other not-yet-replicated associations have been described for genes relevant to drug metabolism and oxidative stress and cytokine genes.


Publication metadata

Author(s): Daly AK

Publication type: Article

Publication status: Published

Journal: Pharmacogenomics

Year: 2010

Volume: 11

Issue: 5

Pages: 607-611

Print publication date: 01/05/2010

ISSN (print): 1462-2416

ISSN (electronic): 1744-8042

Publisher: Future Medicine Ltd.

URL: http://dx.doi.org/10.2217/PGS.10.24

DOI: 10.2217/PGS.10.24


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