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Impact of beta-2 Thr164lle and combined beta-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

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Impact of beta-2 Thr164lle and combined beta-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

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Título Impact of beta-2 Thr164lle and combined beta-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients
Autor Biolo, Andreia
Salvaro, Roberto Gabriel
Clausell, Nadine Oliveira
Ferreira, Daiane Nicoli Silvello dos Santos
Santos, Kátia Gonçalves dos
Rohde, Luis Eduardo Paim
Abstract Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the β2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middleaged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and β2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60%) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with β1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of β2-AR, Gly49Gly of β1-AR and/or Gly389Gly of β1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95%CI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95%CI: 0.02-0.90). These data show that the β2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common β1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.
Contido em Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas. Ribeirão Preto. Vol. 43, n. 6 (jun. 2010), p. 565-571
Assunto Insuficiência cardíaca
Polimorfismo genético
Prognóstico
Receptores adrenérgicos
[en] Adrenergic receptors
[en] Genetic polymorphisms
[en] Heart failure
[en] Prognosis
Origem Nacional
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/28268
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