Tumour necrosis factor α 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. PATIENTS: 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.