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BIBTEX RIS

β-adrenergic receptor polymorphisms in susceptibility, response to treatment and prognosis in heart failure: Implication of ethnicity

2012; Spandidos Publishing; Volume: 7; Issue: 1 Linguagem: Inglês

10.3892/mmr.2012.1120

ISSN

1791-3004

Autores

Sabrina Bernárdez Pereira, Mônica Wanderley Monçores Velloso, Sérgio Chermont, Mônica Maria Pena Quintão, ROSEMERY NUNES ABDHALA, Camila Giro, Thiago Oliveira e Alves, Viviane Camacho, LUIZA DE FÁTIMA MAIA CONTARATO, Felipe Montes Pena, Henrique Miller Balieiro, MARIA LUIZA ROSA GARCIA, Antônio Cláudio Lucas da Nóbrega, Georgina Severo Ribeiro, Evandro Tinoco Mesquita,

Tópico(s)

Receptor Mechanisms and Signaling

Resumo

Common functional polymorphisms in β-adrenergic receptor (βAR) genes have been associated with heart failure (HF) phenotypes and pharmacogenetic interactions with βAR blockers. This study evaluated the association between βAR polymorphisms and carvedilol drug response and prognosis in patients with HF. In this prospective cohort controlled study, 326 volunteers were enrolled [146 HF patients (ejection fraction (EF) <50% by Simpson) and 180 healthy controls]. Drug response was evaluated by echocardiography and outcomes were mortality and hospitalization. DNA was extracted from peripheral blood leukocytes, fragments were amplified by the polymerase reaction and genotyped by restriction fragment length polymorphism (RFLP) for Ser49Gly and Arg389Gly βAR-1 polymorphisms and Gln27Glu and Arg16Gly βAR-2 polymorphisms. The study population was in Hardy‑Weinberg equilibrium. The survival rate was adjusted using the Kaplan-Meier method. HF patients showed the following characteristics: EF 35±9%, 69.9% male, age 59±13 years, 50.7% self-identified as black, 46% had ischemic etiology. The mean follow-up of 23 months showed 18 mortalities and 46 hospitalizations. The genotypes Glu27Glu (24.7 vs. 6.1%, p=0.0004) and Arg16Arg (72.6 vs. 22.8, p<0.0001) of βAR2 polymorphisms and Gly49Gly (33.6 vs. 4.3%, p 20% and βAR polymorphisms. HF patients with β-blocker therapy and the Gly389 allele have reduced event-free survival compared to those carrying the Arg389 allele. Additionally, systolic HF outpatients undergoing β-blocker therapy, self‑identified as black and homozygous for Ser49Ser may have reduced event-free survival, while Glu27Glu, Arg16Arg and Gly49Gly genotypes may be associated with risk for HF.

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