加强非洲人群的大规模药物遗传研究,用于临床护理和药物开发
Abdoulaye Yalcouyé1, Kevin Esoh1,2,3, Ambroise Wonkam1,3
11McKusick-Nathans Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
Annual review of pharmacology and toxicology
|September 22, 2025
概括
非洲人群在基因组研究中代表性不足,限制了药物基因组 (PGx) 洞察力. 更多样化的研究对于个性化医学和全球药物开发至关重要.
科学领域:
- 基因组学就是基因组学.
- 药物基因组学 药物基因组学
- 人口遗传学 人口遗传学
背景情况:
- 非洲人口具有高度的遗传多样性,对药物基因组学 (PGx) 至关重要.
- 在基因组研究中非洲祖先的代表性不足,阻碍了对药物的有效性和毒性的理解.
- 现有的基因组研究,包括全基因组关联研究 (GWASs),缺乏多样性,特别是来自非洲人口.
研究的目的:
- 强调迫切需要对非洲人群进行多样化和包容性的药物基因组研究.
- 强调非洲遗传多样性在推动全球药物开发和个性化治疗方面发挥的关键作用.
- 倡导在非洲人群中应用先进的研究方法,以实现药物基因组学的进步.
主要方法:
- 种群遗传集群化 人口遗传集群化
- 多基因风险得分分析分析分析.
- 高通量有机体模型
- 通过多组学分析.
主要成果:
- 在非洲祖先中普遍存在的PCSK9功能丧失突变为PCSK9抑制剂的发展提供了信息.
- 在全球范围内,PCSK9抑制剂有效降低高胆固醇血症和心血管疾病风险.
- 在不同非洲人群中进行进一步的研究可以显著提高药物基因组学和药物发现.
结论:
- 在非洲人群中进行基因组研究对于全球药物基因组学进步至关重要.
- 利用非洲人口的遗传多样性可以加速药物开发并改善治疗结果.
- 包容性基因组研究是实现全球公平有效个性化医学的关键.
相关概念视频
01:12Analysis of Population Pharmacokinetic Data
682
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
682
01:26Drug Discovery: Overview
11.1K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
11.1K
01:01Dosage Regimens: Partial Pharmacokinetic Parameters
155
It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
155
01:11Clinical Trials: Overview
4.6K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.6K
01:29Therapeutic Drug Monitoring: Affecting Factors
202
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
202
01:28Preclinical Development: Overview
5.8K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.8K