Related Experiment Video
Updated: Jun 26, 2026
07:00
A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity.
S Nagassaki1, R D Herculano, C F O Graeff
1Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
European Journal of Clinical Pharmacology
|December 24, 2008
Summary
Atorvastatin negatively impacts erythrocyte membrane fluidity in individuals with the CC genotype of the T-786C eNOS gene polymorphism. This genetic variation influences how atorvastatin affects red blood cell hemorheology.
Area of Science:
- Pharmacogenomics
- Cardiovascular Research
- Biochemistry
Background:
- Statins, like atorvastatin, exhibit pleiotropic effects, including modulation of endothelial nitric oxide synthase (eNOS).
- A common genetic polymorphism in the eNOS gene promoter (T-786C) may influence individual responses to statins.
- Erythrocyte membrane fluidity is a critical hemorheological property that can be affected by various factors.
Purpose of the Study:
- To investigate whether the T-786C eNOS gene polymorphism modulates the effects of atorvastatin on erythrocyte membrane fluidity.
- To determine if atorvastatin alters hemorheological properties differently based on eNOS genotype.
Main Methods:
- Genotyping of the T-786C polymorphism in 200 healthy subjects.
- Random selection of 15 subjects with TT genotype and 15 with CC genotype for a 14-day treatment with placebo or atorvastatin (10 mg/day).
- Evaluation of erythrocyte membrane fluidity using electron paramagnetic resonance (EPR) and measurement of thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol.
Main Results:
- Atorvastatin significantly reduced erythrocyte membrane fluidity in subjects with the CC genotype (P < 0.05), but not in those with the TT genotype (P > 0.05).
- No significant differences in plasma membrane cholesterol concentrations were observed between genotypes or treatment groups.
- Higher concentrations of TBA-RS were found in CC subjects compared to TT subjects (P < 0.05), indicating increased oxidative stress.
Conclusions:
- The T-786C polymorphism influences atorvastatin's effect on erythrocyte membrane fluidity.
- Short-term atorvastatin treatment appears disadvantageous for hemorheological properties in individuals with the CC genotype compared to the TT genotype.
- These findings highlight the potential role of pharmacogenetics in tailoring statin therapy for optimal cardiovascular outcomes.
Related Concept Videos
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...
01:16Pharmacogenetics 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...
01:29Pharmacogenetic 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...
01:20Lipid-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...
01:28Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
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...