Structural and Functional Impact of Adrenoceptor Beta-1 Gene Polymorphism in Patients with Hypertrophic Cardiomyopathy and Response to Beta-Blocker Therapy

Background: Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiac disorder with diverse clinical presentations. Adrenergic activity, primarily mediated through beta-adrenoceptors, plays a central role in the clinical course of HCM. Adrenergic stimulation increases cardiac contractility and heart rate through beta-1 adrenoceptor activation. Beta-blocker drugs are recommended as the primary treatment for symptomatic HCM patients to mitigate these effects.

Methods: This prospective study aimed to investigate the impact of common ADRB-1 gene polymorphisms, specifically serine–glycine at position 49 and arginine–glycine at position 389, on the clinical and structural aspects of HCM. Additionally, the study explored the association between these genetic variations and the response to beta-blocker therapy in HCM patients.

Results: A cohort of 147 HCM patients was enrolled, and comprehensive assessments were performed. The findings revealed that the Ser49Gly polymorphism significantly influenced ventricular ectopic beats, with beta-blocker therapy effectively reducing them in Ser49 homozygous patients. Moreover, natriuretic peptide levels decreased, particularly in Ser49 homozygotes, indicating improved cardiac function. Left ventricular outflow obstruction, a hallmark of HCM, was also reduced following beta-blocker treatment in all patient groups. In contrast, the Arg389Gly polymorphism did not significantly impact baseline parameters or beta-blocker response.

Conclusion: These results emphasize the role of the Ser49Gly polymorphism in the ADRB-1 gene in shaping the clinical course and response to beta-blocker therapy in HCM patients. This insight may enable a more personalized approach to managing HCM by considering genetic factors in treatment decisions. Further research with larger populations and longer follow-up periods is needed to confirm and expand upon these findings.