影响药物性肝损伤的遗传因素：它们在预防和诊断中起作用吗？
Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis?
作者信息
Clare Kathleen E, Miller Michael H, Dillon John F
机构信息
The GUT Group, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, James Arnott Drive, Dundee, DD1 9SY UK.
出版信息
Curr Hepatol Rep. 2017;16(3):258-264. doi: 10.1007/s11901-017-0363-9. Epub 2017 Aug 7.
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 and amoxicillin/clavulanate DILI has been shown by a number of research groups. The presence of the allele has been associated with an 81-fold increased risk of flucloxacillin DILI. The 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.
综述目的
药物性肝损伤（DILI）的发病机制目前尚不清楚；然而，研究表明某些DILI与基因密切相关。本文描述了全基因组关联研究（GWAS）发现的变异等位基因，并探讨了它们作为易感性生物标志物的潜在作用。
最新发现
多个研究小组已表明[具体基因]与阿莫西林/克拉维酸所致DILI有关联。[具体基因]等位基因的存在与氟氯西林所致DILI的风险增加81倍有关。[具体基因]等位基因与米诺环素所致DILI显著相关。
总结
除用于治疗HIV的阿巴卡韦外，没有其他前瞻性基因筛查试验达到临床应用的阈值。这主要是因为DILI的发病率过低，不值得进行相关检测的成本和投入。也许，随着个性化医疗的发展，可以一次性检测一组与疾病易感性、药物疗效和不良反应相关的基因。这将改变成本效益模式，实现医疗个性化，并通过避免给具有特定人类白细胞抗原（HLA）等位基因的患者用药来降低DILI风险。
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