克罗恩病患者的可变维多利祖马布反应背后的药物基因组途径:一种罕见变异分析
Biljana Stankovic1, Mihajlo Stasuk1, Vladimir Gasic1
1Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia.
Biomedicines
|January 28, 2026
概括
药物基因组标记可以预测克罗恩病中的vedolizumab反应. 脂质代谢和免疫路径的罕见变异区分最佳和次优反应者,指导精准医学.
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
- 胃肠病学 胃肠病学
背景情况:
- 维多利祖马布 (VDZ) 的疗效在克罗恩病 (CD) 患者中有所不同.
- 识别药物基因组 (PGx) 标记对于个性化VDZ治疗至关重要.
- 罕见的遗传变异可能解释不同的治疗反应.
研究的目的:
- 为了确定与CD中低于最佳的VDZ反应相关的PGx通路.
- 为了利用一种罕见变异的分析框架来发现标记物.
- 探索VDZ治疗变异性的遗传基础.
主要方法:
- 用VDZ治疗的63名CD患者的全外体序列测序.
- 在第14周将患者分为最佳响应者 (OR) 和亚最佳响应者 (SR).
- 稀有有害变异过和路径丰富分析 (Reactome数据库).
- 对于罕见变异负担的SKAT-O基因组关联分析.
主要成果:
- 低于最佳的反应与膜运输和胆酸循环通路有关.
- 与MET信号通路相关的最佳反应.
- 显著的脂质代谢途径关联:SRs与促炎/免疫细胞贩运基因 (例如,PIK3CG),ORs与脂肪酸氧化/解毒基因 (例如,ACADM).
结论:
- 基于外体的罕见变异分析可以对CD患者进行VDZ治疗的分层.
- 已识别的基因和通路作为VDZ治疗的潜在PGx标志物.
- 这些发现支持在CD管理中采用精准医学方法.
相关概念视频
Pharmacogenetics and Pharmacogenomics: Overview
Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...


