Tumour necrosis factor alpha gene polymorphism: a predisposing factor to non-ischaemic myocardial dysfunction?
BACKGROUND
Tumour necrosis factor alpha (TNF alpha) is implicated in the pathophysiology of heart failure. Plasma TNF alpha is raised in patients with myocardial dysfunction in proportion to the symptoms.


OBJECTIVE
To determine whether this genetic variant is over represented in heart transplant recipients.


METHODS
175 heart transplant recipients and a control group of 212 healthy volunteers were studied. The reason for transplantation was severe symptomatic myocardial dysfunction in all cases.


METHODS
The TNF alpha genotype was determined by polymerase chain reaction and gel electrophoresis. The populations were compared for their fit to Hardy-Weinberg equilibrium by calculating the expected frequencies of each genotype and comparing them to the observed values. A chi(2) test was used to determine the significance of the difference between the observed and expected values.


RESULTS
No differences were found in the frequency of the TNF2 allele between all heart transplant recipients taken together (54/175, 31%) and healthy volunteers (58/212, 27%). A higher proportion of TNF2 allele carriers was present in cardiac recipients with a pretransplant diagnosis of viral mediated or idiopathic heart failure than in those with ischaemic myocardial dysfunction (26/69 (37.7%) v 28/106 (26.4%), p = 0.03). PATIENTS with a non-ischaemic aetiology had a higher prevalence of TNF2 than healthy volunteers (26/69 (37.7%) v 58/212 (27%), p = 0.05).


CONCLUSIONS
The TNF2 allele is overrepresented in patients with end stage non-ischaemic myocardial dysfunction. This may represent a genetic predisposition in a small subset of patients who could respond favourably to anti-TNF alpha treatment.
Densem
C G
CG
Cardiothoracic Transplant Unit, Wythenshawe Hospital, Manchester, UK School of Biological Sciences, Manchester University, UK.
Hutchinson
I V
IV
Yonan
N
N
Brooks
N H
NH
D015415:Biomarkers; D009202:Cardiomyopathies / Q000235:genetics* / Q000601:surgery; D004587:Electrophoresis, Agar Gel; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016027:Heart Transplantation; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha