Related Experiment Video

Updated: May 15, 2025

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis
04:34

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Published on: June 15, 2011

18.2K

Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or

Liang Shu1, Liyan Sun2, Cong Yu3

  • 1Department of Neurology, Shanghai Ninth People's Hospital, Shanghai, China.

Archives of Medical Science : AMS
|April 7, 2025
PubMed

Insights

Higher protein C levels are genetically linked to an increased risk of deep venous thrombosis (DVT). This association is partially mediated by body mass index, suggesting new avenues for DVT risk identification.

Area of Science:

  • Genetics
  • Thrombosis Research
  • Epidemiology

Background:

  • Observational studies suggest protein C and S influence thrombotic diseases.
  • The "anticoagulation paradox" in deep venous thrombosis (DVT) remains unexplained.
  • Causal links between anticoagulant proteins and DVT risk require elucidation.

Purpose of the Study:

  • To investigate the causal effects of protein C, protein S, and antithrombin-III on DVT risk.
  • To utilize a bidirectional Mendelian randomization (MR) framework for assessing these associations.
  • To explore potential mediation pathways in the protein C-DVT relationship.

Main Methods:

  • Employed a two-sample bidirectional Mendelian randomization (MR) framework.
  • Utilized genome-wide association study data from 484,598 individuals for DVT.
  • Conducted multivariable MR and two-step MR mediation analysis.

Main Results:

  • Protein C showed a significant causal association with increased DVT risk (OR per SD increase: 1.005, p < 0.001).
  • No significant causal associations were found for protein S (OR: 0.997, p = 0.146) or antithrombin-III (OR: 1.001, p = 0.456).
  • Body mass index partially mediated the protein C-DVT association (11.4% mediated proportion).

Conclusions:

  • Genetic variation in protein C levels, not protein S or antithrombin-III, is causally associated with DVT risk.
  • Findings suggest protein C's role in DVT pathogenesis, potentially influenced by BMI.
  • Offers insights for identifying individuals at higher genetic risk for DVT.
Abstract

Keywords:
Mendelian randomizationcausal effectdeep venous thrombosismediating effectprotein C

More Related Videos

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene07:00

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

Published on: April 1, 2019

9.9K
RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells18:30

RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells

Published on: February 13, 2013

21.8K

Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
12.2K
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...
568
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
13.7K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
38.3K
Pedigree Analysis01:35

Pedigree Analysis

Overview
82.6K
Disorders of Hemostasis01:24

Disorders of Hemostasis

Hemostasis, the process that stops bleeding after a blood vessel injury, is crucial for maintaining the integrity of the circulatory system. However, disorders of hemostasis can disrupt this delicate balance, leading to either excessive clotting or bleeding. These disorders can be broadly classified into thromboembolic disorders and bleeding disorders.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
658