Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia

Ruaño, Gualberto; Seip, Richard L.; Windemuth, Andreas; Wu, Alan H.B.; Thompson, Paul D.

doi:10.1016/j.cll.2016.05.010

Cited by 4 publications

(6 citation statements)

References 72 publications

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“…Pharmacogenetic studies of statins have focused mainly on genes in pharmacokinetic and pharmacodynamic pathways, as well as genes involved in lipid metabolism. Polymorphisms in these genes have been associated mainly with variability in statins efficacy and safety and with risk for cardiovascular events (Patel et al, 2014;Alfonsi, Hegele, Gryn, 2016;Leusink et al, 2016;Ruaño et al, 2016).…”

Section: Cholesterol-lowering Drugsmentioning

confidence: 99%

“…LDL receptor mediates the uptake of LDL particles in the cell surface by binding to the apolipoprotein B (ApoB), the structural protein of the very low-density lipoprotein (VLDL) and LDL. Variants in the LDL receptor encoding gene, LDLR, were described to be associated with increased plasma lipids, reduced response to several statins and high risk for cardiovascular events (Gelissen, McLachlan, 2014;Gryn, Hegele, 2014;Leusink et al, 2016;Postmus et al, 2014;Alfonsi, Hegele, Gryn, 2016;Ruaño et al, 2016).…”

Section: Pharmacodynamics-related Genesmentioning

confidence: 99%

“…The gene encoding the ApoE (APOE) has three main alleles (ε2, ε3, and ε4), which encodes ApoE isoforms with different affinities for cell surface receptors. Candidate genes and genome-wide association studies have suggested that APOE polymorphism is as a robust marker of statininduced cholesterol lowering response, but there is not a clear association with cardiovascular events (Gelissen, McLachlan, 2014;Gryn, Hegele, 2014;Patel et al, 2014;Postmus et al, 2014;Leusink et al, 2016;Ruaño et al, 2016).…”

Section: Lipid Metabolism-related Genesmentioning

confidence: 99%

“…Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and the apoB-containing lipoproteins VLDL and LDL. Polymorphisms in CETP have been associated with variability in HDL cholesterol levels and cardiovascular events in patients treated with statins (Patel et al, 2014;Alfonsi, Hegele, Gryn, 2016;Leusink et al, 2016;Ruaño et al, 2016).…”

Section: Reverse Cholesterol Transport-related Genesmentioning

confidence: 99%

“…The endothelial nitric oxide synthase (eNOS) produces the vasodilator nitric oxide (NO), which regulates the vascular system by inhibition of platelet aggregation, leukocyte adhesion and smooth muscle proliferation. Variants in the eNOS encoding gene (NOS3) have been associated with myotoxicity of statins (Gryn, Hegele, 2014;Ruaño et al, 2016).…”

Section: Endothelial Function-related Genesmentioning

confidence: 99%

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Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

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Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

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Section: Cholesterol-lowering Drugsmentioning

confidence: 99%

Section: Pharmacodynamics-related Genesmentioning

confidence: 99%

Section: Lipid Metabolism-related Genesmentioning

confidence: 99%

Section: Reverse Cholesterol Transport-related Genesmentioning

confidence: 99%

Section: Endothelial Function-related Genesmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

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Genetic Risk Factors for Statin-Associated Muscle Symptoms (SAMS)

Rosario

Ducongé

Ruaño

2020

Contemporary Cardiology

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How I Treat statin-associated Side Effects in an Outpatient Setting

Pulipati

Davidson

2021

Future Cardiol.

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Dyslipidemia promotes atherosclerosis and causes cardiovascular diseases. Statins are potent lipid-lowering medications with a cardiovascular mortality benefit. They are generally safe and well tolerated but sometimes can be associated with side effects of variable severity. The most common side effect is statin-associated muscle symptoms. Uncommon side effects include new-onset diabetes mellitus and elevation in liver enzymes. These effects can lead to noncompliance and premature discontinuation of the medication. Hence, it is crucial to identify patients with true statin-associated side effects (SASE) to ensure optimal statin use. The appropriate evaluation of the patient before starting statins and proactive utilization of available diagnostic tests to rule out alternate etiologies mimicking adverse effects are essential for accurate diagnosis of SASE. In patients with true SASE, timely intervention with modified statin or non-statins is beneficial. Herein, we discuss key clinical trial data on statins and non-statins, and describe our center’s approach toward patients with SASE.

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Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia

Cited by 4 publications

References 72 publications

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Genetic Risk Factors for Statin-Associated Muscle Symptoms (SAMS)

How I Treat statin-associated Side Effects in an Outpatient Setting

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