Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK.
Pharmacogenomics. 2010 May;11(5):607-11. doi: 10.2217/pgs.10.24.
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.
药物性肝损伤（DILI）是一种罕见但潜在严重的特异质反应。通过候选基因和全基因组关联研究，自 2000 年以来，已发现 DILI 易感性与 HLA 基因和与药物代谢相关的基因存在复制关联，主要与 HLA 基因和与药物代谢相关的基因存在关联。HLA 关联包括氟氯西林诱导损伤与 I 类等位基因 B*5701 之间的强烈关联，以及与 co-amoxiclav 和 ximelagatran DILI 之间的 II 类基因型较弱的关联。这些关联表明损伤机制涉及免疫反应，可能涉及药物或代谢物与蛋白质的复合物。对于与药物代谢相关的基因，异烟肼 DILI 与 NAT2 缓慢乙酰化之间的最佳复制关联。GSTM1 纯合缺失和/或 GSTT1 纯合缺失等位基因也似乎是 DILI 的一个危险因素，已经独立描述了几种药物的关联。其他尚未复制的关联已在与药物代谢和氧化应激及细胞因子基因相关的基因中描述。
