多基因和药基因组对药物剂量的贡献:现实世界的纵向生物库研究
Silva Kasela1, Laura Birgit Luitva1,2, Kristi Krebs1
1Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
多基因分数和药物基因组 (PGx) 信号都会影响药物剂量变化. 现实世界的电子健康记录证明了在精准医学中个性化处方策略的潜力.
科学领域:
- 药物基因组学 药物基因组学
- 精准医学是一门精准的医学.
- 遗传学 是一个遗传学.
背景情况:
- 药物剂量的个体间变化对于精准医学至关重要.
- 对药物反应的药物遗传学 (PGx) 洞察力是显著的,但对剂量可变性的多基因贡献和用于剂量估计的EHR使用不足.
研究的目的:
- 调查多基因对药物剂量变化的贡献.
- 评估电子健康记录 (EHR) 对估计维持药物剂量的有用性.
主要方法:
- 利用来自爱沙尼亚生物银行 (N=212,000) 的纵向药物购买数据来确定个人每日,中位数和最大药物剂量.
- 通过使用线性混合模型和多变量回归,评估了16种特征和药物剂量的多基因分数 (PGS) 之间的关联.
- 对已知的PGx基因进行了全基因组关联研究 (GWAS) 和基因组丰富分析.
主要成果:
- 特定特征的PGS显著预测了他类药物的每日剂量 (冠状动脉心脏病PGS) 和甲醇 (静缩血压PGS).
- 体重指数PGS与每日服用他类药物,美托普罗罗尔和华法林有关.
- GWAS证实了已知的metoprolol (CYP2D6) 和华法林 (CYP2C9,VKORC1) 的药基因组学信号,PGx loci.的独立贡献.
结论:
- 证明了使用现实世界EHR数据来导出药物剂量表型的可行性和价值.
- 强调了多基因和药基因组因素都会导致剂量变化.
- 强调了这些遗传因素在开发个性化处方策略方面的潜力.
更多相关视频
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
08:21Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations
Published on: July 21, 2023
相关概念视频
Analysis of Population Pharmacokinetic Data
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Factors Affecting Drug Response: Overview
Factors Affecting Protein-Drug Binding: Patient-Related Factors
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Factors Affecting Drug Biotransformation: Biological
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
