Related Experiment Video

Updated: May 28, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
07:00

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL

James P Corsetti1, Dan Ryan, Arthur J Moss

  • 1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. James_Corsetti@urmc.rochester.edu

Thrombosis and Haemostasis
|October 21, 2011
PubMed

Insights

Thrombospondin-4 (TSP-4) genetic variants are linked to recurrent coronary risk in high-risk patients. This matricellular protein influences vascular inflammation and cardiovascular disease (CVD) risk, particularly in those with high HDL cholesterol and CRP levels.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Molecular Biology

Background:

  • Vascular inflammation and oxidative stress impact high-density lipoprotein (HDL) functionality, contributing to cardiovascular disease (CVD) risk.
  • Limited human studies explore the interplay between HDL dysfunction and CVD risk.
  • High-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) identify high-risk post-infarction patients.

Purpose of the Study:

  • Investigate the role of Thrombospondin-4 (TSP-4) in cardiovascular disease (CVD) risk.
  • Analyze the association of a functional genetic polymorphism in THBS4 (TSP-4) with recurrent coronary events.
  • Examine the relationship between TSP-4, vascular inflammation, and established genetic risk factors (CYBA, CETP).

Main Methods:

  • Multivariable modeling was used to assess CVD risk associated with the THBS4 A387P polymorphism (rs1866389).
  • Functional genetic polymorphisms in CYBA (C242T, rs4673) and CETP (TaqIB, rs708272) were analyzed.
  • Blood markers, including von Willebrand factor and D-dimer, were measured in post-infarction patients.

Main Results:

  • The gain-of-function P-allele of the THBS4 polymorphism showed a significant risk association (HR 2.00, p=0.024).
  • In high-risk patients with the P-allele, von Willebrand factor correlated with D-dimer levels, suggesting endothelial dysfunction and thrombogenesis.
  • TSP-4 was identified as a key player in recurrent coronary risk in specific patient subgroups.

Conclusions:

  • Thrombospondin-4 (TSP-4) plays a role in recurrent coronary risk for post-infarction patients with high HDL-C and CRP.
  • The THBS4 A387P polymorphism is a risk factor for recurrent cardiovascular events.
  • Further research is needed on vascular inflammation's effects on HDL particle functionality.

Related Concept Videos

Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
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...
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
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...
Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT01:25

Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT

Calcium-Scoring CT ScanA calcium-scoring CT scan, also known as coronary artery calcium (CAC) scan, detects calcium deposits in the coronary arteries. This test assesses the risk of coronary artery disease (CAD), which can lead to cardiovascular events such as angina, heart failure, and sudden cardiac arrest.A calcium-scoring CT scan is generally recommended for individuals at intermediate risk of CAD without symptoms. It includes:Men aged 40-75 and women aged 50-75: Especially those with a...
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...