关于他类药物治疗和降低胆固醇的药物遗传学研究
Daniel I Chasman1, David Posada, Lakshman Subrahmanyan
1Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02215, USA.
JAMA
|June 17, 2004
概括
在HMG-CoA减少酶基因的遗传变异可以降低pravastatin的有效性. 具有特定基因变异的个体可能会从这种他类药物治疗中看到较小的胆固醇降低.
科学领域:
- 药物遗传学 药物遗传学
- 脂质代谢 脂质代谢是什么
- 心血管遗传学 心血管遗传学
背景情况:
- 影响药物反应的遗传变异可能会影响治疗疗效.
- 脂质代谢基因中的多态性可能会影响他类药物的有效性.
研究的目的:
- 系统地评估遗传变异是否影响对普拉瓦斯塔丁治疗的反应.
- 调查单核酸多态 (SNPs) 与普拉瓦斯塔丁疗效之间的关联.
主要方法:
- 在10个候选基因中对148个SNP进行了普拉瓦斯塔丁治疗的1536个个体的DNA分析.
- 检查了基因变异和24周内脂质水平变化之间的关联.
主要成果:
- 在HMG-CoA减少酶基因中,有两种常见的SNP与减少普拉瓦斯塔丁疗效有关.
- 与同卵性个体相比,异卵性个体的总和LDL胆固醇减少明显较小.
- 没有发现HDL胆固醇变化或基线脂质水平的相关性.
结论:
- 在HMG-CoA减少酶基因的遗传变异可以减少普拉瓦斯塔丁的降胆固醇效应.
- 患有特定HMG-CoA减少酶基因变异的个体可能会从pravastatin治疗中获得较少的益处.
相关概念视频
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
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...
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...


