ABC | Volume 114, Nº4, April 2020

Original Article Ser49Gly Beta1-Adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure Felipe Neves de Albuquerque, 1, 2 Andrea Araujo Brandão, 1 Dayse Aparecida Silva , 3 R icardo Mourilhe Rocha, 1 Marcelo Imbroinise Bittencourt, 1 Ana Luiza Ferreira Sales , 1 Pedro Pimenta de Mello Spineti, 1 Gustavo Salgado Duque, 1 Lucas Rangel de Souza Azevedo , 1 Roberto Pozzan, 1 Bernardo Rangel Tura, 4 Denilson Campos de Albuquerque, 1 Universidade do Estado do Rio de Janeiro, 1 Rio de Janeiro, RJ – Brazil Hospital Samaritano, 2 Rio de Janeiro, RJ – Brazil Universidade do Estado do Rio de Janeiro - Instituto de Biologia, 3 Rio de Janeiro, RJ – Brazil Instituto Nacional de Cardiologia – Arritmia, 6 Rio de Janeiro, RJ – Brazil Mailing Address: Felipe Neves de Albuquerque • Universidade do Estado do Rio de Janeiro – Cardiologia - Boulevard 28 de Setembro, 77, 2º andar. Postal Code 20550-900, Rio de Janeiro, RJ - Brazil E-mail: felipenalbuquerque@gmail.com , felipe.albuquerque@uerj.br Manuscript received March 20, 2019, revised manusacript June 04, 2019, accepted June 05, 2019 DOI: https://doi.org/10.36660/abc.20190187 Abstract Background: The role of Ser49Gly beta1-adrenergic receptor genetic polymorphism (ADBR1-GP-Ser49Gly) as a predictor of death in heart failure (HF) is not established for the Brazilian population. Objectives: To evaluate the association between ADBR1-GP-Ser49Gly and clinical outcomes in individuals with HF with reduced ejection fraction. Methods: Secondary analysis of medical records of 178 patients and genotypes of GPR β 1-Ser49Gly variants, classified as Ser-Ser, Ser-Gly and Gly-Gly. To evaluate their association with clinical outcome. A significance level of 5% was adopted. Results: Cohort means were: clinical follow-up 6.7 years, age 63.5 years, 64.6% of men and 55.1% of whites. HF etiologies were predominantly ischemic (31.5%), idiopathic (23.6%) and hypertensive (15.7%). The genetic profile was distributed as follows: 122 Ser-Ser (68.5%), 52 Ser‑Gly (28.7%) and 5 Gly-Gly (2.8%). There was a significant association between these genotypes and mean NYHA functional class at the end of follow-up (p = 0.014) with Gly-Gly being associated with less advanced NYHA. In relation to the clinical outcomes, there was a significant association (p = 0.026) between mortality and GPR β 1-Ser49Gly: the number of deaths in patients with Ser-Gly (12) or Gly-Gly (1) was lower than in those with Ser-Ser (54). The Gly allele had an independent protective effect maintained after multivariate analysis and was associated with a reduction of 63% in the risk of death (p = 0.03; Odds Ratio 0.37 – CI 0.15–0.91). Conclusion: The presence of β 1-AR-GP Gly-Gly was associated with better clinical outcome evaluated by NYHA functional class and was a predictor of lower risk of mortality, regardless of other factors, in a 6.7-year of follow-up. (Arq Bras Cardiol. 2020; 114(4):613-615) Keywords: Heart Failure/mortality;Epidemiology; Polymorfism, Geetic; Receptors,Adreneic, beta; cardiovascular Dieases; Hospitalization; Epinephrine/therapeutic use; Cardiotoxicity. Introduction Heart failure (HF) is currently the main cause of hospital admissions due to circulatory diseases in the Brazilian public healthcare system: 202,000 patients were admitted in 2018, costing BRL 311 million. 1 The current strategy with clinical, laboratory and imaging parameters to predict prognosis is limited. The natural history of HF is unpredictable, even in phenotypically similar patients. The therapies available are capable of reducing mortality by up to 60%, 2 but response to these medical treatments is heterogeneous. It has been demonstrated that genetic nature influences this variability. 3-5 In the pathophysiology of HF, the role of the Sympathetic Nervous System (SNS) is well established. Cardiac beta1- adrenergic receptor (R β 1) is the main structure responsible for mediating the effects of adrenaline. Sustained stimulation of this system determines multiple deleterious effects, 3 especially cardiotoxicity. 6 Accordingly, some genetic variants that modified the activity of this receptor have been described. A genetic polymorphism (GP) was identified at position 145 of the nucleotide that resulted in the substitution of Serine for Glycine at position 49 of the amino acid – GPR β 1-Ser49Gly. 7 GPR β 1-Ser49Gly was associated with a dramatic interference with R β 1 function. The Gly allele determined greater reduction in its number (down-regulation) compared 616