Pharmacogenomics of Heart Failure: a Systematic Review

Mottet, Fannie; Vardeny, Orly; Denus, Simon de

doi:10.2217/pgs-2016-0118

Cited by 10 publications

(8 citation statements)

References 229 publications

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“…β‐blockers have shown significantly reduced mortality rates in heart failure patients and is the cornerstone in prevention of sudden cardiac death in long QT syndrome (LQTS) patients . β‐blockers have thus in heart failure shown “marked beneficial effects, on cardiac function, morbidity, and survival” . The clinical effects are, however, affected by significant intraclass and interpatient variability …”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Ågesen

Weeke

Tfelt‐Hansen

et al. 2019

Pharmacology Res & Perspec

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The aim of this study was to evaluate the pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology by reviewing single‐dose and steady‐state pharmacokinetic studies from the literature. PubMed was searched for pharmacokinetic studies of beta‐adrenergic blocking agents, both single‐dose and steady‐state studies. The studies included reported maximum plasma concentration (C max ) and/or area under the concentration curve (AUC). The coefficient of variation (CV%) was calculated for all studies, and a CV% <40% was considered low or moderate variability, and a CV% >40% was considered high variability. The C max and AUC were reported a total of 672 times in 192 papers. Based on AUC, metoprolol, propranolol, carvedilol, and nebivolol showed high pharmacokinetic variability (highest first), whereas bisoprolol, atenolol, sotalol, labetalol, nadolol, and pindolol showed low to moderate variability (lowest first). We have shown a high interindividual pharmacokinetic variability that varies markedly in different beta‐adrenergic blocking agents; the extreme being steady state ratios as high as 30 in metoprolol. A more personalized approach to the medical treatment of patients may be obtained by combining known pharmacokinetic information about variability, pharmaco‐genetics and ‐dynamics, and patient characteristics, to avoid adverse events or lack of treatment effect.

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Section: Introductionmentioning

confidence: 99%

“…β‐blockers have thus in heart failure shown “marked beneficial effects, on cardiac function, morbidity, and survival” . The clinical effects are, however, affected by significant intraclass and interpatient variability …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Ågesen

Weeke

Tfelt‐Hansen

et al. 2019

Pharmacology Res & Perspec

View full text Add to dashboard Cite

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“…We were able to replicate the association of the index SNP rs1801253 with birth weight in the ADRB1 gene, which codes for the β1-adrenergic receptor protein that is highly expressed in lungs, heart, and brain, and mediates the action of catecholamines in the sympathetic nervous system (Mottet et al 2016). The birth weight-lowering minor G-allele has higher frequency in African ancestry populations compared to European ancestry populations (0.43 vs 0.32, respectively).…”

Section: Discussionmentioning

confidence: 91%

Admixture mapping and fine-mapping of birth weight loci in the Black Women’s Health Study

et al. 2018

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Several genome-wide association studies (GWAS) have identified genetic variants associated with birth weight. To date, however, most GWAS of birth weight have focused primarily on European ancestry samples even though prevalence of low birth weight is higher among African-Americans. We conducted admixture mapping using 2918 ancestral informative markers in 2596 participants of the Black Women's Health Study, with the goal of identifying novel genomic regions where local African ancestry is associated with birth weight. In addition, we performed a replication analysis of 11 previously identified index single nucleotide polymorphisms (SNPs), and fine-mapped those genetic loci to identify better or new genetic variants associated with birth weight in African-Americans. We found that high African ancestry at 12q14 was associated with low birth weight, and we identified multiple independent birth weight-lowering variants in this genomic region. We replicated the association of a previous GWAS SNP in ADRB1 and our fine-mapping efforts suggested the presence of new birth weight-associated variants in ADRB1, HMGA2, and SLC2A4. Further studies are needed to determine whether birth weight-associated loci can in part explain race-associated birth weight disparities.

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“…There are multiple accounts of these genetic polymorphisms resulting in resistant strains of malaria because of abnormalities in metabolism [ 112 , 113 , 114 ]. These same gene polymorphisms affect heart failure patients since the CYP 2D6 gene is responsible for the metabolism of metoprolol [ 115 , 116 ]. This polymorphism affect many other drugs such as Isoniazid (INH), barbiturates, omeprazole, selective serotonin reuptake inhibitors (SSRI’s), sulfasalazine, hydralazine, etc.…”

Section: Cytochrome 2d6 Genetic Polymorphisms Covid-19mentioning

confidence: 99%

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm

et al. 2020

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Coronaviruses are very large RNA viruses that originate in animal reservoirs and include severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) and other inconsequential coronaviruses from human reservoirs like the common cold. SARS-CoV-2, the virus that causes COVID-19 and is believed to originate from bat, quickly spread into a global pandemic. This RNA virus has a special affinity for porphyrins. It invades the cell at the angiotensin converting enzyme-2 (ACE-2) receptor and binds to hemoproteins, resulting in a severe systemic inflammatory response, particularly in high ACE-2 organs like the lungs, heart, and kidney, resulting in systemic disease. The inflammatory response manifested by increased cytokine levels and reactive oxygen species results in inhibition of heme oxygenase (HO-1), with a subsequent loss of cytoprotection. This has been seen in other viral illness like human immunodeficiency virus (HIV), Ebola, and SARS/MERS. There are a number of medications that have been tried with some showing early clinical promise. This illness disproportionately affects patients with obesity, a chronic inflammatory disease with a baseline excess of cytokines. The majority of the medications used in the treatment of COVID-19 are metabolized by cytochrome P450 (CYP) enzymes, primarily CYP2D6. This is further complicated by genetic polymorphisms of CYP2D6, HO-1, ACE, and ACE-2. There is a potential role for HO-1 upregulation to treat/prevent cytokine storm. Current therapy must focus on antivirals and heme oxygenase upregulation. Vaccine development will be the only magic bullet.

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Pharmacogenomics of Heart Failure: a Systematic Review

Abstract: Given the rising prevalence of HF and related costs, a more personalized use of HF drugs could have a remarkable benefit for patients, caregivers and healthcare systems.

Cited by 10 publications

References 229 publications

Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Admixture mapping and fine-mapping of birth weight loci in the Black Women’s Health Study

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm

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