Abstract
Background -Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.Methods -We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.Results -During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ2 = 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.Conclusion -In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.
Highlights
Genetic polymorphisms have been studied with the hypotheses of influencing presentation, course and prognosis of patients with heart failure [1]
For polymorphism Thr164Ile, 97% of the samples were homozygous for the Thr164Thr genotype and 3% heterozygous for Thr164Ile; this polymorphism was excluded from further analysis by the low frequency of heterozygous genotypes
The distribution of genotypes of polymorphism Arg16Gly was statistically significant relative to body mass index analyzed as an ordinal variable (χ2 = 9.797; p = 0.04, being genotype Arg/Arg associated with a higher frequency of a BMI above 25), but not when it was analyzed as a continuous variable (BMI mean values (SD): Arg/Arg 26.32 (5.75), Arg/Gly 25.61 (5.44), Gly/Gly 25.14 (5.13); p = 0.34); no significant difference was observed for genotypes of polymorphism Gln27Glu
Summary
Genetic polymorphisms have been studied with the hypotheses of influencing presentation, course and prognosis of patients with heart failure [1]. In patients harboring alleles Gly and Glu, previoulsy associated with increased down regulation of beta-2 adrenergic receptors, a statistically significant difference relative to prognosis has not been demonstrated. The polymorphisms Thr164Ile, Arg16Gly and the haplotypes with alleles Gly and Gln were associated with reduced exercise tolerance in other study that enrolled 232 patients with idiopathic dilated cardiomyopathy or ischemic cardiomyopathy [3]. These findings substantiate the hypotheses that polymorphisms Arg16Gly, Gln27Glu and Thr164Ile of beta-2 receptor gene might be functional and might be associated with differences in the survival rate of patients with heart failure. Due to sparse and sometimes conflicting results, this hypothesis deserves further testing in different populations
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