Apolipoprotein A-V Genetic Variation and Plasma Lipoprotein Response to Fibrates

Hegele, Robert A.; Pollex, Rebecca L.

doi:10.1161/atvbaha.107.144980

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…The average decrease was significantly greater in APOA5 56 G carriers than non-carriers (35.8% vs. 27.9% decreases, P = 0.006). An accompanying editorial heralded its potential contribution to personalized medicine 83 . There is, however, an alternative interpretation of Lai et al 's results from the perspective of quantile-dependent expressivity.…”

Section: Discussionmentioning

confidence: 99%

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Williams

2020

Sci Rep

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Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations paul t. Williams "Quantile-dependent expressivity" is a dependence of genetic effects on whether the phenotype (e.g., triglycerides) is high or low relative to its distribution in the population. Quantile-specific offspringparent regression slopes (β op) were estimated by quantile regression for 6227 offspring-parent pairs. Quantile-specific heritability (h 2), estimated by 2β op /(1 + r spouse), decreased 0.0047 ± 0.0007 (P = 2.9 × 10 −14) for each one-percent decrement in fasting triglyceride concentrations, i.e., h 2 ± Se were: 0.428 ± 0.059, 0.230 ± 0.030, 0.111 ± 0.015, 0.050 ± 0.016, and 0.033 ± 0.010 at the 90th, 75th, 50th, 25th, and 10th percentiles of the triglyceride distribution, respectively. Consistent with quantile-dependent expressivity, 11 drug studies report smaller genotype differences at lower (posttreatment) than higher (pre-treatment) triglyceride concentrations. This meant genotype-specific triglyceride changes could not move in parallel when triglycerides were decreased pharmacologically, so that subtracting pre-treatment from post-treatment triglyceride levels necessarily created a greater triglyceride decrease for the genotype with a higher pre-treatment value (purported precision-medicine genetic markers). In addition, sixty-five purported gene-environment interactions were found to be potentially attributable to triglyceride's quantile-dependent expressivity, including gene-adiposity

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Section: Discussionmentioning

confidence: 99%

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Williams

2020

Sci Rep

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“…Compared to non-carriers, APOA5 56G carriers demonstrated a more pronounced decrease in fasting triglycerides (-36% vs -28%, p = 0.006) and increase in HDL-cholesterol (+12% vs +7%, p = 0.002) after 3 weeks of fenofibrate therapy. 96,97 Following a fat load, a significant decrease in postprandial triglycerides was observed among 56G carriers compared to non-carriers, as well. 96,97 The weight of data argues against the use of fibrates to address residual cardiovascular risk in the majority of statin-treated patients.…”

Section: Genotyping To Assess Efficacy Of Non-statin Lipid-lowering Dmentioning

confidence: 95%

Personalized vascular medicine: Individualizing drug therapy

et al. 2011

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Personalized medicine refers to the application of an individual’s biological fingerprint – the comprehensive dataset of unique biological information – to optimize medical care. While the principle itself is straightforward, its implementation remains challenging. Advances in pharmacogenomics as well as functional assays of vascular biology now permit improved characterization of an individual’s response to medical therapy for vascular disease. This review describes novel strategies designed to permit tailoring of four major pharmacotherapeutic drug classes within vascular medicine: antiplatelet therapy, antihypertensive therapy, lipid-lowering therapy, and antithrombotic therapy. Translation to routine clinical practice awaits the results of ongoing randomized clinical trials comparing personalized approaches with standard of care management.

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“…8 Fenofibrate acts by reducing plasma triglyceride levels by up to 40% below their baseline level 9 and increasing the HDL cholesterol level. 10 The lipid-modifying effects of fenofibrate are not completely understood, but its effects are known to be mediated by the activation of the nuclear transcription factor peroxisome proliferator-activated receptor-a (PPARa), which in turn modifies other genes involved in lipid metabolism through the heterodimer formed with RXR. [11][12][13][14][15] Blood is one of the most easily available materials in humans, which makes it ideal for the detection of markers and analytical analysis.…”

Section: Introductionmentioning

confidence: 99%

“…Pharmacological treatment of HTG involves the use of fenofibrate . Fenofibrate acts by reducing plasma triglyceride levels by up to 40% below their baseline level and increasing the HDL cholesterol level . The lipid‐modifying effects of fenofibrate are not completely understood, but its effects are known to be mediated by the activation of the nuclear transcription factor peroxisome proliferator‐activated receptor‐a (PPARα), which in turn modifies other genes involved in lipid metabolism through the heterodimer formed with RXR …”

Section: Introductionmentioning

confidence: 99%

Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome

Moreno-Indias

Tinahones

Clemente‐Postigo

et al. 2017

Clinical Endocrinology

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Apolipoprotein A-V Genetic Variation and Plasma Lipoprotein Response to Fibrates

Cited by 10 publications

References 34 publications

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Personalized vascular medicine: Individualizing drug therapy

Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome

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