Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients
Braz. j. med. biol. res
;
43(6): 565-571, June 2010. ilus, tab
Article
in English
| LILACS
| ID: lil-548267
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 middle-aged 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 percent) 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 percentCI 0.17-0.95) and HF-related mortality (HR 0.12, 95 percentCI 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Polymorphism, Genetic
/
Heart Failure
Type of study:
Etiology study
/
Incidence study
/
Observational study
/
Prognostic study
/
Risk factors
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2010
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Federal do Rio Grande do Sul/BR
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