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NLRP3 is associated with coronary artery disease in Vietnam veterans
Wole Akosile1, Joanne Voisey2, Bruce Lawford2
1School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes, Queensland 4120, Australia.
Insights
The Nod Like Receptor family pyrin domain containing 3 (NLRP3) polymorphism, specifically rs10159239, is linked to higher coronary calcium scores. This finding suggests a potential genetic role for NLRP3 in coronary artery disease development.
Area of Science:
- Cardiovascular Science
- Genetics
- Immunology
Background:
- Coronary artery disease (CAD) is linked to inflammation, with elevated pro- and anti-inflammatory cytokines observed.
- The inflammasome NLRP3 (Nod Like Receptor family pyrin domain containing 3) is increasingly implicated in CAD aetiology.
- Higher NLRP3 expression correlates with increased CAD severity, prompting investigation into NLRP3 polymorphisms.
Purpose of the Study:
- To investigate the association between NLRP3 polymorphisms and coronary artery disease.
- To determine if specific NLRP3 genetic variations contribute to the development or severity of CAD.
Main Methods:
- Analysis of NLRP3 polymorphisms in a cohort of 299 Vietnam War veterans with prior trauma exposure.
- Association analysis between NLRP3 polymorphisms and coronary calcium scores using ANOVA and independent t-tests.
- Exploration of dominant/recessive models and Hardy-Weinberg Equilibrium calculation.
Main Results:
- The NLRP3 polymorphism rs10159239 showed a significant association (p=0.001) with higher coronary calcium scores.
- Logistic regression confirmed rs10159239's significance (p=0.035) when adjusted for known CAD risk factors.
- This is the first study to associate the rs10159239 A-allele with elevated coronary calcium.
Conclusions:
- The rs10159239 A-allele is significantly associated with increased coronary calcium scores.
- This finding highlights a potential genetic link between NLRP3 and coronary artery disease.
- Further validation in larger cohorts is recommended to confirm these results.
Background:
Previous studies have established that coronary artery disease is associated with excess inflammation. These studies have shown an elevation of both pro and anti-inflammatory cytokines in sufferers of coronary artery disease. There is increasing interest in the role played by the inflammasome Nod Like Receptor family pyrin domain containing 3 (NLRP3) in the aetiology of coronary artery disease. Increased severity of coronary artery disease correlates with higher levels of expression of NLRP3. Does NLRP3 polymorphisms play a role in the aetiology of coronary artery disease?
Method:
In a cohort of Vietnam War (n-299) veterans who have been previously exposed to trauma, NLRP3 polymorphisms were analysed for association with coronary calcium scores using analyses of variance. Independent t-test was used to analyse genotypes. In samples with a small representation of minor homozygotes, genotypes were combined and analysed using independent t-test. If any of the genotype analysis suggested the potential for a dominant or a recessive model the model was further explored. Hardy-Weinberg Equilibrium was calculated using Hardy-Weinberg equilibrium calculator including analysis for ascertainment bias.
Results:
The NLRP3 polymorphism, rs10159239 was significantly associated (p = 0.001) with a higher raised coronary calcium score. The Single Nucleotide Polymorphism rs10159239 was examined by logistic regression with known risk factors for Coronary artery disease and remained significant (0.035). This is the first time rs10159239 A-allele has been associated with raised coronary calcium score.
Conclusions:
This is the first time rs10159239 A-allele has been associated with raised coronary calcium score. Further research is needed to replicate our results in larger well-characterised cohorts.
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