Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Developmental Medicine, King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
DNA Cell Biol. 2020 Mar;39(3):349-354. doi: 10.1089/dna.2019.4982. Epub 2020 Jan 6.
The liver is susceptible to drug toxicity due to its vital role in xenobiotic metabolism and elimination. In addition to human leukocyte antigen (HLA) variants, which were previously determined as risk factors for drug-induced liver injury (DILI) due to co-amoxiclav, other non-HLA genes may contribute to hepatotoxicity risk. In this study, the association between DILI due to co-amoxiclav and several non-HLA genes was investigated. Association of variants in candidate genes ( and ) with DILI due to various drugs was reported previously in other DILI cohorts. This study examined relevance in a co-amoxiclav-DILI cohort. One hundred sixty-five co-amoxiclav DILI cases were recruited from several European countries by two different studies (DILIGEN and iDILIC). A North-East England population group ( = 334) was used as the control group. PCR assays were used to genotype for the and null alleles with TaqMan SNP genotyping assays used for (rs4880) and (rs1050450). Fisher's exact test was used to assess differences in significance between cases and controls. None of the studied variants ( rs4880, rs1050450, null allele, and null allele) was significantly associated with co-amoxiclav DILI compared with the control group. No significant differences between cases and controls were seen when combined genotypes and genotypes were considered. Despite the possible functional relevance and the previously reported contribution of the selected genes to DILI, our study failed to confirm associations between the selected genes and liver injury induced by co-amoxiclav.
肝脏易受到药物毒性的影响，因为它在异生物质代谢和消除中起着至关重要的作用。除了先前被确定为阿莫西林克拉维酸钾引起的药物性肝损伤（DILI）风险因素的人类白细胞抗原（HLA）变体之外，其他非 HLA 基因也可能导致肝毒性风险。在这项研究中，研究了与阿莫西林克拉维酸钾相关的几种非 HLA 基因与药物性肝损伤的关系。先前在其他 DILI 队列中报道了候选基因（和）中的变体与各种药物引起的 DILI 之间的关联。本研究在阿莫西林克拉维酸钾引起的 DILI 队列中检验了其相关性。通过两项不同的研究（DILIGEN 和 iDILIC），从几个欧洲国家招募了 165 例阿莫西林克拉维酸钾引起的 DILI 病例。一个英格兰东北部人群（ = 334）作为对照组。使用 TaqMan SNP 基因分型检测进行聚合酶链反应（PCR）检测，用于 （rs4880）和 （rs1050450）的 等位基因和 缺失等位基因。Fisher 精确检验用于评估病例组和对照组之间差异的显著性。与对照组相比，研究中没有发现研究的任何变体（rs4880、rs1050450、缺失等位基因和缺失等位基因）与阿莫西林克拉维酸钾引起的 DILI 显著相关。当考虑联合 基因型和 基因型时，病例组和对照组之间未见显著差异。尽管这些选定的基因具有潜在的功能相关性和先前报道的对 DILI 的贡献，但我们的研究未能证实这些选定的基因与阿莫西林克拉维酸钾引起的肝损伤之间的关联。
