β(1)- and α(2c)-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry

BACKGROUND: Although the β,(1)-adrenoreceptor (AR) Gly389Arg and α(2C)-AR Del322-325 gene variants are associated with the response to β-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 polymorphism-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 β-AR-blockers (not indicated as standard care at the time of completing this study). RESULTS: All patients and controls genotyped for the α(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 α(2c)-AR variant, the β(1)-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving β-AR-blockers.