Fibrate Pharmacogenomics: Expanding Past the Genome

House, John S.; Motsinger‐Reif, Alison A.

doi:10.2217/pgs-2019-0140

Cited by 8 publications

(6 citation statements)

References 114 publications

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“…Fibrates are a drug class with lipid-modifying properties used to lower blood triglyceride levels and raise high-density lipoprotein cholesterol levels. The response to fibrate treatment is also PGx related [118] (Table 2).…”

Section: Antithrombotic Drugs Vitamin K Antagonistsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Antithrombotic Drugs Vitamin K Antagonistsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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“…Interestingly, this variant was associated with lower levels of circulating CCL11, which is a proinflammatory and atherogenic cytokine [31]. Fibrate pharmacogenomics have been reviewed in detail by House & Motsinger-Reif [32]. The identification of PPARA common variants, which are associated with a clear cardiovascular benefit from fibrate treatment, justifies additional clinical studies.…”

Section: Peroxisome Proliferator Activated Receptor Alpha (Pparα)mentioning

confidence: 99%

Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease

Wagner

2023

IJMS

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Peroxisome proliferator activated receptors, including PPARα, PPARβ/δ, and PPARγ, are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They play important roles in glucose and lipid metabolism and are also supposed to reduce inflammation and atherosclerosis. All PPARs are involved in angiogenesis, a process critically involved in cardiovascular pathology. Synthetic specific agonists exist for all PPARs. PPARα agonists (fibrates) are used to treat dyslipidemia by decreasing triglyceride and increasing high-density lipoprotein (HDL) levels. PPARγ agonists (thiazolidinediones) are used to treat Type 2 diabetes mellitus by improving insulin sensitivity. PPARα/γ (dual) agonists are supposed to treat both pathological conditions at once. In contrast, PPARβ/δ agonists are not in clinical use. Although activators of PPARs were initially considered to have favorable effects on the risk factors for cardiovascular disease, their cardiovascular safety is controversial. Here, we discuss the implications of PPARs in vascular biology regarding cardiac pathology and focus on the outcomes of clinical studies evaluating their benefits in cardiovascular diseases.

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“…In parallel, production of Apo A-I and ABCA 1 is up-regulated (Steiner, 2007). Pharmacogenomic studies show that response to fibrates could be influenced by polymorphisms in PPAR-α, Apo E, Apo A-I, Apo B, Apo C-III, Apo AV, IL-6 and LPL genes (House and Motsinger-Reif, 2020). Furthermore, the efficacy of fibrates could also be affected by epigenetic modifications, specifically methylation levels, on the gene CEMIP2, which codifies a cell-surface transmembrane protein (House and Motsinger-Reif, 2020).…”

Section: Fibratesmentioning

confidence: 99%

“…Pharmacogenomic studies show that response to fibrates could be influenced by polymorphisms in PPAR-α, Apo E, Apo A-I, Apo B, Apo C-III, Apo AV, IL-6 and LPL genes (House and Motsinger-Reif, 2020). Furthermore, the efficacy of fibrates could also be affected by epigenetic modifications, specifically methylation levels, on the gene CEMIP2, which codifies a cell-surface transmembrane protein (House and Motsinger-Reif, 2020). Fibrates have been shown to be capable of increasing cholesterol efflux to HDL in animal models (Balendiran et al, 2007;Fournier et al, 2013).…”

Section: Fibratesmentioning

confidence: 99%

High density lipoprotein as a therapeutic target: Focus on its functionality

ROSSO,

DAVICO,

CHIAPPE

et al. 2023

BIOCELL

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Cardiovascular diseases (CVDs) are the leading cause of death globally. CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease and rheumatic heart disease among other conditions. There are multiple independent risk factors for CVD, including hypertension, age, smoking, insulin resistance, elevated low-density lipoprotein cholesterol (LDL-C) levels, and triglyceride levels. LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk. High density lipoprotein (HDL) constitutes the only lipoprotein fraction with atheroprotective functions. Early HDL-targeted therapies have focused on increasing HDL-C levels. However, clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction. A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition, leading to loss of functionality. As a result, targeting HDL-C levels would be insufficient to achieve CVD risk reduction, making HDL functionality a more desirable focus for HDL-directed therapies. There are several drugs which show the potential to improve HDL functionality. These drugs include molecules already approved for human use, such as statins and niacin, and particularly, compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL preparations. These therapies show promising potential to improve HDL functionality specifically. Future therapeutic strategies should incorporate HDL functionality as a main target of interest.

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Fibrate Pharmacogenomics: Expanding Past the Genome

Cited by 8 publications

References 114 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease

High density lipoprotein as a therapeutic target: Focus on its functionality

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