Ser49Gly Beta1-Adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure. / O Polimorfismo Genético do Receptor Beta-Adrenérgico Tipo 1 Ser49Gly é Preditor de Morte em Pacientes Brasileiros com Insuficiência Cardíaca.

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 GPRß1-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 GPRß1-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 ß1-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).

O Polimorfismo Genético do Receptor Beta-Adrenérgico Tipo 1 Ser49Gly é Preditor de Morte em Pacientes Brasileiros com Insuficiência Cardíaca / Ser49Gly Beta1-Adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure

Resumo Fundamento O papel do polimorfismo genético do receptor beta1-adrenérgico Ser49Gly (PG-Rβ1-Ser49Gly) como preditor de eventos na insuficiência cardíaca (IC) não está definido para a população brasileira. Objetivos Avaliar a relação entre PG-Rβ1-Ser49Gly e desfechos clínicos em indivíduos com IC com fração de ejeção reduzida. Métodos Análise secundária de prontuários de 178 pacientes e identificação das variantes do PG-Rβ1-Ser49Gly, classificadas como Ser-Ser, Ser-Gly e Gly-Gly. Avaliar sua relação com evolução clínica. Foi adotado nível de significância de 5%. Resultados As médias da coorte foram: seguimento clínico, 6,7 anos; idade, 64,4 anos; 63,5% de homens e 55,1% brancos. A etiologia da IC foi predominantemente isquêmica (31,5%), idiopática (23,6%) e hipertensiva (15,7%). O perfil genético teve a seguinte distribuição: 122 Ser-Ser (68,5%), 52 Ser-Gly (28,7%), e 5 Gly-Gly (2,8%). Houve relação significativa entre esses genótipos e a classe funcional da New York Heart Association (NYHA) ao final do acompanhamento (p = 0,014) com o Gly-Gly associado a NYHA menos avançada. Com relação aos desfechos clínicos, houve associação significativa (p = 0,026) entre mortalidade e PG-Rβ1-Ser49Gly: o número de óbitos em pacientes com Ser-Gly (12) ou Gly-Gly (1) foi menor que com Ser-Ser (54). O alelo Gly teve um efeito protetor independente mantido após análise multivariada e foi associado à redução na chance de óbito de 63% (p = 0,03; odds ratio 0,37 - IC 0,15 a 0,91). Conclusão A presença do PG-Rβ1 Gly-Gly associou-se a melhor evolução clínica avaliada pela classe funcional da NYHA e foi preditor de menor risco de mortalidade, independentemente de outros fatores, em seguimento de 6,7 anos. (Arq Bras Cardiol. 2020; 114(4):616-624)

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 GPRβ1-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 GPRβ1-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 β1-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)