The G-308A Polymorphism of the TNF-? Gene Does not Predict Changes in Cardiac Function in Response to Medical Therapy for Idiopathic Dilated Cardiomyopathy

ABSTRACT

The G-308A polymorphism of the tumour necrosis factor-? (TNF-?) gene; a variant that influences TNF-? transcription; may contribute to non-ischaemic dilated cardiomyopathy. To evaluate whether TNF-? genotyping may assist in identifying a subset of patients who could potentially benefit from immunomodulatory therapy; we assessed the relationship between the G-308A polymorphism of the TNF-? gene and changes in left ventricular (LV) chamber dimensions and systolic function in patients with idiopathic dilated cardiomyopathy (IDC) before and six months after diuretic; digoxin and angiotensin-converting enzyme inhibitor (ACEI) therapy. In 331 patients with IDC and 349 controls; the TNF-2 (A) allele (odds ratio = 1.509; 95CI = 1.130-2.015; p 0.01) and the TNF-12/22 (AG/GG) genotype (odds ratio CI = 1.159-2.266; p 0.01) were associated with IDC. However; in 122 patients with IDC; the TNF-? genotype was not associated with plasma TNF-? concentrations. In 133 patients with IDC; the TNF-? genotype failed to predict either the severity of pump dysfunction and cardiac dilatation at baseline; or changes in pump function and cardiac dimensions after six months of medical treatment. We conclude therefore that although the TNF-? gene G-308A polymorphism may contribute to the development of IDC; it does not influence pump function or adverse cardiac remodelling in patients with IDC. Genotyping for this variant is therefore unlikely to assist in identifying patients with heart failure who may be particularly susceptible to novel immunomodulatory therapeutic strategies