Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

Biolo, Andréia; Salvaro, Roberto Gabriel; Clausell, Nadine Oliveira; Silvello, Daiane; Santos, Kátia Gonçalves dos; Rohde, Luís Eduardo Paim

doi:10.1590/s0100-879x2010007500052

Cited by 9 publications

(7 citation statements)

References 30 publications

(39 reference statements)

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“…In general, the present results regarding the two polymorphisms in ADRB1 are in accordance with those obtained from previous studies by our research group in other cohorts of patients with HF with ischemic and non-ischemic etiology (39)(40)(41). In the first study by Biolo et al (39), the Ser49Gly polymorphism was reported to not be associated with non-sustained VT on Holter monitoring or death.…”

Section: Discussionsupporting

confidence: 93%

Non‑synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all‑cause death in patients with non‑ischemic heart failure

Telles,

May,

Pimentel

et al. 2023

Exp Ther Med

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Sudden cardiac death (SCD) is an unpredictable and common mode of death in patients with heart failure (HF). Alterations in calcium handling may lead to malignant arrhythmias, resulting in SCD, and variants in calcium signaling-related genes have a significant association with SCD. Therefore, the aim of the present retrospective cohort study was to investigate the association of Ser96Ala [histidine-rich calcium-binding protein (HRC)], Ser49Gly [β1-adrenergic receptor (ADRB1)], Arg389Gly (ADRB1) and Gly1886Ser [ryanodine receptor 2 (RYR2)] polymorphisms with serious arrhythmic events and overall mortality in patients with HF with reduced left ventricular ejection fraction of non-ischemic etiology. In total, 136 patients with HF underwent physical examination, routine laboratory tests, non-invasive assessment of cardiac function and an invasive electrophysiological study. The primary outcome was the occurrence of serious arrhythmic events, set as either SCD or appropriate implantable cardioverter-defibrillator (ICD) therapy, and the secondary outcome was all-cause death. During a median follow-up of 37 months, arrhythmic events occurred in 26 patients (19%) and 41 patients (30%) died. Patients carrying the Ser allele of the Ser96Ala polymorphism in HRC had worse survival than those with the Ala/Ala genotype (log-rank P=0.043). Despite the difference in survival time, the Ala/Ala genotype was not associated with all-cause death in the regression analysis [unadjusted hazard ratio (HR)=0.17; 95% CI, 0.02-1.21]. Regarding the Ser49Gly and Arg389Gly polymorphisms in ADRB1, homozygosity for the major alleles at both sites (Ser49Ser and Arg389Arg) was associated with a two-fold increased risk of all-cause death compared with the other genotype combinations (unadjusted HR=1.98; 95% CI, 1.02-3.82). However, this association was lost after controlling for clinical covariates. No association was observed for the Gly1886Ser polymorphism in RYR2. Overall, the present findings are concurrent with the hypothesis that the Ser96Ala (HRC), Ser49Gly (ADRB1) and Arg389Gly (ADRB1) polymorphisms may be associated with HF prognosis. In particular, the Ser96Ala polymorphism might aid in risk stratification and patient selection for ICD implantation.

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Section: Discussionsupporting

confidence: 93%

Non‑synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all‑cause death in patients with non‑ischemic heart failure

Telles,

May,

Pimentel

et al. 2023

Exp Ther Med

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“…Specifically, the genetic impact is different between epidemiologic and intervention studies with β-blockers. In the β-blocker ‘naïve’ state, the Gly389X genotype group was reported to have a better prognosis and greater survival [ 18 , 29 ]. In contrast, there was a report that suggested lack of benefit of the Gly389 allele [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

Lee

Chung

Jeon

et al. 2016

Korean J Intern Med

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Background/Aims:We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF).Methods:One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year.Results:Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the β-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 ± 14.3 to 70.0 ± 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 ± 2.62 mg vs. 3.96 ± 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group.Conclusions:The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring β-blocker therapy according to genotype.

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“…From all the above results, we concluded that patients carrying Gly389 gene are more likely to gain more pronounced therapeutic effects of β blocker, better improvement of cardiac function and more promising prognosis.Similarly, another Korean study published in 2016 found that Gly389 carriers weremore sensitive to bisoprolol and had better prognosis comparing with patients with Arg389Arg(9). Biolo A et al found that Gly389 carriers had better prognosis and higher survival rate in 2008(13) and 2010(14). Also, HF-ACTION DNA substudyshowed that patients with Arg389Arg allele need higher dosage of β blocker than other genotypes in CHF patients(15).…”

Section: Discussionmentioning

confidence: 99%

Association of Arg389Gly β1-adrenergic receptor polymorphism with effective dose of β blocker in congestive heart failure among Chinese Han population

Shen

Liu

et al. 2018

Preprint

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BackgroundTo investigate the relationship between β1-adrenergic receptor (ADRB1) gene polymorphisms and the response to medication in patients with congestive heart failure (CHF).Methods and ResultsTwo hundred and sixty patients with CHF were enrolled. Ser49Gly and Arg389Gly polymorphisms were identified. During one-year follow-up, differences of echocardiographic parameters and major adverse cardiac events (MACE) were analyzed. For Ser49Gly polymorphisms, there were no differences between AA genotype and AG/GG genotype of baseline clinical features and echocardiographic parameters as well as one-year incidence of MACE. For Arg389Gly polymorphisms, there were no significant differences in baseline clinical characteristics, LVDd and LVEF among the three genotypes. However, the increase amplitude of LVEF after one year among patients carrying GG genotype was significantly higher than those carrying CC genotype (11.7% vs 1.3%, P<0.05). The incidence of MACE among different genotypes of CC, CG and GG were 22.2%, 10.0% and 8.3%,with statistical difference (P=0.021).ConclusionsThe study suggested there was no relationship between Ser49Gly polymorphisms of the ADRB1 gene and the therapeutic effect and prognosis in CHF patients under the same dosage of drugs. However, the improvement of cardiac function and prognosis in patients carrying the Gly389 allele were significantly better than those of Arg389Arg homozygous.

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Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

Cited by 9 publications

References 30 publications

Non‑synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all‑cause death in patients with non‑ischemic heart failure

Non‑synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all‑cause death in patients with non‑ischemic heart failure

Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

Association of Arg389Gly β1-adrenergic receptor polymorphism with effective dose of β blocker in congestive heart failure among Chinese Han population

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