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Updated: Aug 2, 2026

On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Polymorphisms in the TNF-alpha and TNF-receptor genes in patients with coronary artery disease
R A Allen1, E M Lee, D H Roberts
1Blackpool Victoria Hospital, Whinney Heys Road, Blackpool, UK.
Insights
Genetic variations in tumor necrosis factor-alpha (TNF-alpha) and its receptors are not linked to coronary artery disease (CAD). This study found no association between these gene polymorphisms and the development or severity of CAD.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Immunology
Background:
- Coronary artery disease (CAD) is a complex condition influenced by multiple genes and environmental factors.
- Atheroma formation, a key feature of CAD, involves inflammation, with tumor necrosis factor-alpha (TNF-alpha) playing a significant role.
- Investigating genetic variations in TNF-alpha and its receptors could reveal insights into CAD pathogenesis.
Purpose of the Study:
- To examine the association between specific polymorphisms in the TNF-alpha, TNF receptor 1, and TNF receptor 2 genes and the presence of CAD.
- To determine if these genetic variations correlate with the extent of coronary artery disease (single-vessel vs. multivessel).
Main Methods:
- Genotyping of TNF-alpha (-238, -308), TNF receptor 1 (-609, +10), and TNF receptor 2 (+422) polymorphisms using PCR-RFLP analysis.
- Comparison of allele and genotype frequencies between patients with confirmed CAD (single and multivessel) and control groups (normal coronary arteries and healthy volunteers).
- Meta-analysis of published studies on TNF-alpha gene polymorphisms (-308 and -238) combined with the current study's data.
Main Results:
- No significant differences in allele or genotype frequencies were observed for any of the studied polymorphisms between CAD patients and control groups.
- No association was found between TNF-alpha gene polymorphisms and the severity of CAD (single-vessel vs. multivessel disease).
- A meta-analysis combining current data with previous studies did not reveal any significant association between TNF-alpha gene polymorphisms (-308 and -238) and CAD.
Conclusions:
- Polymorphisms in the TNF-alpha promoter region are not associated with the development of coronary artery disease.
- Genetic variations in TNF receptor 1 and TNF receptor 2 genes do not appear to be linked to CAD development.
Background:
Coronary artery disease (CAD) is both multifactorial and polygenic in nature. Atheroma formation, the pathological hallmark of CAD, is an inflammatory process, with pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), having a major role in its pathogenesis. We have therefore investigated whether polymorphisms in the TNF-alpha (- 238 and - 308), TNF receptor 1 (position - 609 and + 10, intron 6) and TNF receptor 2 (position + 422, codon 198) genes show an association with CAD.
Materials And Methods:
Patients with angiographically proven single vessel (n = 58) and multivessel (n = 122) CAD were compared to patients with angiographically proven normal coronary arteries (n = 79) and volunteers without clinical evidence of CAD (n = 250). Genotyping was performed by PCR-RFLP analysis. For the TNF-alpha polymorphisms, a meta-analysis of all published studies was also undertaken.
Results:
No significant differences in allele or genotype frequencies were found between the normal coronary artery group or healthy volunteers and patients with CAD for any of the polymorphisms. There was also no difference in allele frequency between patients with single- and multivessel disease. For the - 308 and - 238 TNRalpha gene polymorphisms, a meta-analysis of our data and previously published studies failed to demonstrate any significant association with CAD.
Conclusions:
Polymorphisms in the TNF-alpha promoter region and TNF-receptor genes are not associated with the development of CAD.
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