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Tumour necrosis factor alpha gene polymorphism: a predisposing factor to non-ischaemic myocardial dysfunction?
C G Densem1, I V Hutchinson, N Yonan
1Cardiothoracic Transplant Unit, Wythenshawe Hospital, Manchester, UK School of Biological Sciences, Manchester University, UK.
Heart (British Cardiac Society)
|January 18, 2002
Summary
The TNF2 genetic variant is more common in heart transplant recipients with non-ischemic heart failure. This finding suggests a potential genetic predisposition and may inform future anti-TNF alpha therapies.
Area of Science:
- Cardiovascular Genetics
- Immunology
- Transplantation Science
Background:
- Tumor Necrosis Factor alpha (TNF alpha) plays a role in heart failure pathophysiology.
- Elevated plasma TNF alpha levels correlate with symptom severity in myocardial dysfunction.
- Genetic variations in TNF alpha may influence susceptibility to heart failure.
Purpose of the Study:
- To investigate the prevalence of the TNF2 genetic variant in heart transplant recipients.
- To determine if TNF2 allele is overrepresented in patients undergoing heart transplantation.
Main Methods:
- Genotyping for TNF alpha was performed using polymerase chain reaction and gel electrophoresis.
- Heart transplant recipients (n=175) and healthy volunteers (n=212) were analyzed.
- Chi-squared tests and Hardy-Weinberg equilibrium calculations were used for population comparison.
Main Results:
- No significant difference in TNF2 allele frequency was observed between all heart transplant recipients and healthy controls.
- A higher proportion of TNF2 allele carriers was found in recipients with viral or idiopathic heart failure compared to those with ischemic heart failure (p=0.03).
- Patients with non-ischemic heart failure showed a higher prevalence of the TNF2 allele than healthy volunteers (p=0.05).
Conclusions:
- The TNF2 allele is overrepresented in patients with end-stage non-ischemic myocardial dysfunction.
- This genetic finding may indicate a predisposition in a subset of patients.
- The results suggest potential benefits from anti-TNF alpha treatment in these patients.