Unravelling Sex Differences in Drug‐Induced Liver Injury

General, Applied and Systems Toxicology Pub Date : 2011-09-15 DOI:10.1002/9780470744307.GAT226

W. Tong, Q. Shi, W. Salminen, Minjun Chen, H. Fang, A. Suzuki, D. Mendrick

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引用次数: 1

Abstract

Liver toxicity accounts for 40% of failed drugs in clinical studies and approximately 21% of drugs that are removed from the market. It is suspected that drug-induced liver injury (DILI) is more common in females, thus impacting women's health to a higher degree. However, it is unclear how common this potential sex-based sensitivity may be and the mechanisms underlying the differences. High-content and high-throughput molecular technologies such as DNA microarrays have contributed significantly to the understanding of health and disease at the molecular level. In 2001, DNA microarray studies began to emerge to investigate sex-associated liver gene expression profiles under physiological and pathological conditions. This review is an analysis of clinical reports published to date to determine the weight of evidence in support of sex-biased sensitivity to DILI. Sex differences related to disease susceptibility/progression and adverse drug events are discussed at the molecular level with emphasis on genomic data in an attempt to place the evidence in a biological context. Keywords: DILI; sex difference; genomics; drug-induced liver injury

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揭示药物性肝损伤的性别差异

肝毒性占临床研究失败药物的40%，约占从市场上撤下的药物的21%。推测药物性肝损伤(DILI)在女性中更为常见，对女性健康的影响程度更高。然而，目前尚不清楚这种基于性别的潜在敏感性有多普遍，以及这种差异背后的机制。DNA微阵列等高含量和高通量分子技术对在分子水平上了解健康和疾病作出了重大贡献。2001年，DNA微阵列研究开始出现，以研究生理和病理条件下与性别相关的肝脏基因表达谱。本综述是对迄今为止发表的临床报告的分析，以确定支持DILI性别偏见敏感性的证据权重。与疾病易感性/进展和药物不良事件相关的性别差异在分子水平上进行了讨论，重点是基因组数据，试图将证据置于生物学背景下。关键词:帝力;性别差异;基因组学;药物性肝损伤

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General, Applied and Systems Toxicology

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