非欧洲患者的DPYD遗传多态性与重度胺相关的毒性:一个系统性审查
Tsun Ho Chan1, J Eunice Zhang1, Munir Pirmohamed2
1Wolfson Centre for Personalised Medicine, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 1-5 Brownlow Street, Liverpool, L69 3GL, UK.
British journal of cancer
|June 17, 2024
概括
治疗前的DPYD查在英国和欧盟是强制性的,以减少胺的毒性. 本次审查强调了非欧洲人群中的DPYD变异,建议扩大查以提高患者安全性和减少健康不平等.
科学领域:
- 药物基因组学 药物基因组学
- 临床化学 临床化学
背景情况:
- 目前英国和欧盟的指导方针要求对二皮里米丁脱酶 (DPYD) 进行查,以防止严重的皮里米丁毒性.
- 现有的查主要集中在欧洲人口中普遍存在的四种常见DPYD变异.
研究的目的:
- 系统地审查非欧洲血统患者的DPYD变异.
- 评估已识别的DPYD变体的临床相关性和功能预测.
- 为更广泛的DPYD查协议提供建议.
主要方法:
- 按照PRISMA指南进行系统审查,搜索文章至2023年4月.
- 提取DPYD变体的in silico功能预测和体外功能数据.
- 对于所有已识别的DPYD变体进行in silico预测分析.
主要成果:
- 32项研究评估了5个种族 (非洲裔美国人,东亚人,拉丁美洲人,中东人,南亚人) 的53种DPYD变体.
- 欧洲变种c.1905+1G>A在南亚,东亚和中东的患者中发现,这些患者经历了严重的毒性.
- 在非洲血统的人群中普遍存在的c.557A>G变种显示出强有力的证据,但不在英国小组中.
结论:
- 扩大DPYD查以包括非欧洲祖先群体中发现的变异对患者安全至关重要.
- 包括这些变体将有助于减轻不同人群中与胺相关的严重毒性.
- 加强查可以减少种族差异的健康差异在种族多样化的社会.
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