Beta1- and ? 2c-Adrenoreceptor Variants as Predictors of Clinical Aspects of Dilated Cardiomyopathy in People of African Ancestry : Cardiovascular Topics

Background : Although the Beta1-adrenoreceptor (AR) Gly389Arg and ?2c-AR Del322-325 gene variants are associated with the response to Beta-AR-blocker therapy; whether this effect is associated with the risk for heart failure; or the severity or progression of heart failure is uncertain. Aims : To assess the relationship between Gly389Arg and Del322-325 variants and the presence; severity and progression of idiopathic dilated cardiomyopathy (IDC) in 403 black South African patients. Methods : Genotypes were identified using a restriction fragment length olymorphism-based technique and automated sequencing. Left ventricular ejection fraction (LVEF) and dimensions were determined at baseline and in 132 patients after six months of standard medical therapy excluding Beta- AR-blockers (not indicated as standard care at the time of completing this study). Results : All patients and controls genotyped for the ?2c-AR variant were homozygous for the Del322-325 (risk) allele. The Gly389Arg polymorphism was not associated with IDC (control n = 429) (Arg389 allele homozygosity : odds ratio = 1.03; confidence limits = 0.78-1.35); nor did it predict LVEF and cavity dimensions either before or after therapy. Conclusion : in patients homozygous for the risk allele of the ?2c-AR variant; the Beta1-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving Beta-AR-blockers

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

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