Related Experiment Video
Updated: Jun 21, 2026
09:15
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Genetic polymorphisms of low density lipoprotein receptor can modify stroke presentation
Jiann-Der Lee1, Ya-Hui Lin, Huan-Lin Hsu
1Department of Neurology, Chang Gung Memorial Hospital, Chiayi, Chang Gung University, Taoyuan, Taiwan.
Neurological Research
|July 11, 2009
Summary
Genetic variations in the low-density lipoprotein receptor (LDLR) gene are linked to small vessel occlusion (SVO) stroke risk. Specific LDLR gene polymorphisms increase SVO risk, while a particular haplotype may reduce it in Taiwanese patients.
Area of Science:
- Neuroscience
- Genetics
- Cardiovascular Research
Background:
- Low-density lipoprotein (LDL) transport across the blood-brain barrier is mediated by the LDL receptor (LDLR).
- LDLR expression in brain capillary endothelial cells suggests its role as a susceptibility gene influencing stroke presentation.
- Genetic factors affecting LDLR function may impact cerebrovascular disease risk and outcomes.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) and haplotypes in the LDLR gene and the risk of small vessel occlusion (SVO) disorder.
- To determine if LDLR genetic variations modify stroke presentation in a Taiwanese population.
Main Methods:
- A case-control study involving 292 cerebral infarction patients, including 76 with SVO and 216 with non-SVO disorders.
- Haplotype-tagging SNP association analysis was performed using HapMap data in an isolated Taiwanese population.
- Statistical analysis included calculating odds ratios (ORs) and confidence intervals (CIs) for specific genotypes (rs2738446, rs2738450) and haplotypes.
Main Results:
- The homozygote CC genotype for rs2738446 was associated with a two-fold increased risk of SVO disorder (OR=2.0, p=0.025).
- The homozygote CC genotype for rs2738450 showed a 1.85-fold increased risk of SVO disorder (OR=1.85, p=0.04).
- The GA haplotype, using the common CC haplotype as reference, was associated with a 48% decreased risk of SVO disorder (OR=0.52, p=0.029).
Conclusions:
- Genetic polymorphisms in the LDLR gene are associated with small vessel occlusion (SVO) stroke risk.
- Specific LDLR genotypes (CC for rs2738446 and rs2738450) increase SVO risk.
- Haplotype analysis suggests that LDLR genetic variations can modify stroke presentation, with the GA haplotype potentially offering a protective effect against SVO.
Related Concept Videos
01:29Pharmacogenetic 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...
01:29Pharmacogenomics: 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...
01:11Pharmacogenetics 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...
01:27Pharmacogenetics 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...
01:16Pharmacogenetics 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...
01:20Lipid-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...