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Blood Studies for Cardiovascular System III: Serum Lipid Profile01:25

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Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Related Experiment Video

Updated: Dec 27, 2025

Assessing Whole-Body Lipid-Handling Capacity in Mice
07:57

Assessing Whole-Body Lipid-Handling Capacity in Mice

Published on: November 24, 2020

4.6K

Quantile-dependent expressivity of postprandial lipemia.

Paul T Williams1

  • 1Lawrence Berkeley National Laboratory, Berkeley, CA, United States of America.

Plos One
|February 27, 2020
PubMed
Summary

Quantile-dependent expressivity shows that genetic effects on triglyceride levels intensify with higher concentrations. This phenomenon explains gene-drug interactions, challenging traditional gene-environment interaction models.

Area of Science:

  • Genetics
  • Metabolic Disorders
  • Pharmacogenomics

Background:

  • Genotype effects on phenotypes can vary with trait levels, a phenomenon termed quantile-dependent expressivity.
  • Previous research suggests genetic risk scores (GRS) for triglyceride levels are more impactful at higher concentrations.
  • Postprandial lipemia, a state of elevated triglycerides after a meal, is ideal for studying quantile-dependent expressivity.

Purpose of the Study:

  • To investigate quantile-dependent expressivity in genetic variants influencing postprandial triglyceride levels.
  • To determine if genetic effect sizes increase with triglyceride concentrations.
  • To explore if this phenomenon explains interactions with sex, diet, disease, BMI, and drugs.

Main Methods:

  • Analyzed 97 published papers containing triglyceride response and genotype data.

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Related Experiment Videos

Last Updated: Dec 27, 2025

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  • Extracted quantitative data from graphs plotting mean triglyceride response versus time and genotype.
  • Used standard least-squares regression to assess the relationship between genotype differences and average triglyceride concentrations over time.

    • Main Results:

    • Genetic effect sizes for numerous polymorphisms (e.g., ABCA1, APOE, CETP, LPL) significantly increased with rising triglyceride concentrations (P≤0.05).
    • A dose-response relationship was observed, with intermediate effects at intermediate triglyceride levels.
    • Quantile-dependent expressivity offered an alternative explanation for interactions traditionally attributed to gene-environment interactions and personalized medicine.

    Conclusions:

    • Quantile-dependent expressivity is prevalent for genetic variants affecting postprandial triglycerides.
    • Impaired variant functionality likely exacerbates at higher triglyceride levels, driving this phenomenon.
    • Apparent gene-drug interactions may be manifestations of quantile-dependent expressivity, not solely predictors of drug efficacy.