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Pharmacogenomics. 2010 May;11(5):607-11. doi: 10.2217/pgs.10.24.

Drug-induced liver injury: past, present and future.

Author information

1
Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. a.k.daly@ncl.ac.uk

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.

PMID:
20415545
DOI:
10.2217/pgs.10.24
[Indexed for MEDLINE]

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