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Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations
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Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations

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A multi-centre observational cohort study on pharmacogenomic predictors of rosuvastatin discontinuation in a

Mais N Alqasrawi1, Zeina N Al-Mahayri2, Lubna Q Khasawneh1

  • 1Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.

Frontiers in Pharmacology
|September 15, 2025
PubMed

Insights

Genetic variants in ABCG2 impact rosuvastatin adherence. The ABCG2 rs2231142 variant significantly increases discontinuation risk, highlighting its role in personalized cardiovascular risk reduction therapy.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Rosuvastatin is a key drug for cardiovascular risk reduction, but patient adherence is often limited.
  • Genetic variations, especially in ABCG2 and SLCO1B1 genes, affect how patients respond to rosuvastatin.
  • The ABCG2 rs2231142 variant is linked to increased drug efficacy but also a higher risk of side effects like muscle problems.

Purpose of the Study:

  • To investigate how ABCG2 rs2231142 and SLCO1B1 rs4149056 genetic variants influence rosuvastatin discontinuation.
  • To assess the impact of these variants on LDL cholesterol levels in a multiethnic population.
  • To evaluate the potential for personalized rosuvastatin therapy based on genetic profiles.

Main Methods:

  • A 12-month prospective cohort study involving 422 adults prescribed rosuvastatin.
  • Collection of discontinuation data through medical records and phone calls.
  • Genotyping using TaqMan SNP assays, followed by Cox regression, Kaplan-Meier, and logistic regression analyses.

Main Results:

  • The ABCG2 rs2231142 T/T genotype showed a significantly higher risk of rosuvastatin discontinuation (HR = 4.40, p < 0.001).
  • Patients who discontinued rosuvastatin experienced worsening LDL cholesterol levels (+21.89%) compared to continuers (-17.86%).
  • The ABCG2 variant was more prevalent in patients who discontinued the medication (30.6% vs. 17.4%, p = 0.0026).

Conclusions:

  • Carriers of the ABCG2 minor allele face an elevated risk of discontinuing rosuvastatin, likely due to adverse effects.
  • Genetic testing for the ABCG2 variant could enable personalized rosuvastatin treatment strategies.
  • Identifying high-risk individuals through genetic screening may improve patient adherence and long-term cardiovascular outcomes.
Abstract

Keywords:
ABCG2 rs2231142personalized medicinepharmacogenomicsrosuvastatinstatin discontinuation

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