The role of adrenergic receptor polymorphisms in heart failure

Abstract

The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of ß-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.

Os polimorfismos dos receptores adrenérgicos na insuficiência cardíaca: o que a genética explica?

“…These same studies demonstrated that this variant is related to an improvement in the hemodynamic activity and ventricular function in response to beta-blocking, which demonstrates the importance of such studies for the development of more effective and personalized therapies 15 .…”

“…Studies with the Arg389Gly polymorphism did not show an association with the survival rate 15 . Table 1 summarizes the main effects of the beta-1 adrenergic receptor polymorphisms on prognosis and the response to beta-blockers in HF.…”

Polymorphic Variants of Genes Coding Sympathoadrenal System Influence on Phenotype of Patients With Hypertrophic Cardiomyopathy

“…Опубликованы немногочисленные данные по изучению ассоциации между клиническим течением хронической сердечной недостаточности (ХСН) и полиморфизмом генов, кодирующих β1-АР и β2-АР [12][13][14]. Так, L. Covolo et al [15] на европей-ской популяции и S. Nonen et al [16] на японской популяции не обнаружили ассоциативных взаимо-связей между полиморфизмом Arg389Glu гена ADRB1 и риском развития ХСН.…”

“…По результатам бразильских исследователей -A. Biolo et al [12], варианты генетического полимор-физма Arg389Gly гена ADRB1, как и варианты поли-морфизма Ser49Gly гена ADRB1, не влияли на степень выраженности ХСН. Однако у лиц с вариантом поли-морфизма Gly389 значимо чаще выявлялись желу-дочковые нарушения ритма.…”

Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

“…Genetic AR polymorphisms have been associated with the functional modulation of these receptors, as well as with the development, progression, exercise response, and prognosis of HF patients (15)(16)(17)(18). A polymorphism of the β2-AR at position 164 (Thr164Ile) has been described, and the 164Ile allele seems to modulate cardiac contractility negatively (19,20).…”