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Ser49Gly Beta1-Adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure
Felipe Neves de Albuquerque1,2, Andrea Araujo Brandão1, Dayse Aparecida Silva3
1Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Insights
The Ser49Gly beta1-adrenergic receptor genetic polymorphism (ADBR1-GP-Ser49Gly) is linked to better outcomes in Brazilian heart failure patients. The Gly allele offers protection against mortality, reducing death risk by 63%.
Area of Science:
- Cardiology
- Genetics
- Pharmacogenomics
Background:
- The prognostic role of the Ser49Gly beta1-adrenergic receptor genetic polymorphism (ADBR1-GP-Ser49Gly) in heart failure (HF) remains unclear in Brazil.
- Understanding genetic influences on HF outcomes is crucial for personalized medicine.
Purpose of the Study:
- To investigate the association between ADBR1-GP-Ser49Gly variants and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF).
- To determine if the Gly allele confers a protective effect against mortality in this population.
Main Methods:
- Secondary analysis of medical records from 178 HFrEF patients.
- Genotyping of ADBR1-GP-Ser49Gly variants (Ser-Ser, Ser-Gly, Gly-Gly).
- Evaluation of associations between genotypes and clinical outcomes, including mortality and NYHA functional class, over a 6.7-year follow-up.
Main Results:
- The Gly-Gly genotype was associated with a less advanced NYHA functional class at follow-up (p = 0.014).
- A significant association was found between mortality and ADBR1-GP-Ser49Gly (p = 0.026).
- Patients with Ser-Gly or Gly-Gly genotypes had lower mortality rates compared to Ser-Ser.
- The Gly allele demonstrated an independent protective effect, reducing the risk of death by 63% (p = 0.03; OR 0.37).
Conclusions:
- The presence of the β1-AR-GP Gly-Gly genotype is associated with better clinical outcomes, including improved NYHA functional class.
- The Gly allele of ADBR1-GP-Ser49Gly acts as a significant predictor of lower mortality risk in HFrEF patients, independent of other factors.
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).
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