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Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

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...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

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...
Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

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 of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

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...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Pharmacogenetics of Drug Metabolism: Overview01:27

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...

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Updated: Jun 6, 2026

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
06:47

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation

Published on: January 28, 2021

Translating Lipoprotein Genetics Into New Therapies.

Robert A Hegele1

  • 1Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Circulation Research
|June 4, 2026
PubMed
Summary
This summary is machine-generated.

Human genetics identifies drug targets for lowering lipids, with rare variants proving key for therapeutic success. This approach has led to new drug approvals and informed future cardiovascular disease treatments.

Keywords:
RNA, small interferingapolipoproteinscholesteroldyslipidemiasgenomicsoligonucleotides, antisensetriglycerides

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Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
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Area of Science:

  • Human genetics and pharmacology
  • Cardiovascular disease research
  • Drug discovery and development

Background:

  • Human genetics, particularly rare loss-of-function variants, serves as a powerful tool for identifying lipid-lowering drug targets.
  • The 'human knockout' paradigm, observing individuals with genetic variants, provides real-world proof-of-concept for therapeutic targets.
  • Previous genetic insights have validated targets like PCSK9, APOC3, and ANGPTL3, leading to approved therapies.

Purpose of the Study:

  • To review the role of human genetics in identifying and validating targets for lipid-lowering therapies.
  • To discuss the translation of genetic findings into pharmacological interventions, including RNA-based approaches.
  • To assess the current landscape and future potential of genetic insights in cardiovascular drug development.

Main Methods:

  • Analysis of monogenic family studies and population-based sequencing to identify functional genetic variants.
  • Review of Mendelian randomization studies to distinguish causal targets from biomarkers.
  • Examination of RNA-based pharmacology (siRNAs, ASOs) and gene-editing technologies for therapeutic translation.

Main Results:

  • Genetic validation has driven approvals for drugs targeting PCSK9, APOC3, and ANGPTL3, demonstrating significant clinical benefits.
  • Mendelian randomization identified high-density lipoprotein (HDL) cholesterol as a non-causal biomarker, explaining the failure of HDL-raising therapies.
  • RNA-based therapies are emerging as a practical platform for translating genetic targets into durable treatments.

Conclusions:

  • Human genetics is pivotal in discovering and validating lipid-lowering drug targets, significantly impacting cardiovascular medicine.
  • RNA-based pharmacology represents a successful translation of genetic insights into novel therapeutic strategies.
  • While GWAS and polygenic scores expand target discovery, rare-variant genetics currently offers greater translational yield.