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

作者：Mais N. Alqasrawi, Zeina N. Al-Mahayri, Lubna Q. Khasawneh, Areej S. Albawa’neh, Lilas Dabaghie, Sahar M. Altoum, Dana Hamza, Salahdein Aburuz, Virendra Misra, Gohar Jamil, Husam Ouda, Faiz Al-Bakshy, Khuzama AlAhamad, Mohammad M. AlAhmad, Fatma Al‐Maskari, Juma Alkaabi, George P. Patrinos, Bassam R. Ali · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1656520 · 被引用次数：4 · 研究领域：Lipoproteins and Cardiovascular Health、Pharmacogenetics and Drug Metabolism、Genetic Associations and Epidemiology

Background Rosuvastatin is widely used for cardiovascular risk reduction, but treatment discontinuation limits its long-term benefit. Genetic variants, particularly in ABCG2 and SLCO1B1 , influence rosuvastatin’s transport, efficacy, and tolerability. The ABCG2 rs2231142 variant is associated with enhanced efficacy due to increased systemic exposure; however, it also raises the risk of adverse effects, especially muscle-related symptoms. Evaluating the impact of these variants in a real-world, multiethnic population is essential to improving adherence and guiding personalized therapy. The aim of this study is to investigate the influence of ABCG2 rs2231142 (G>T; Q141K) and SLCO1B1 rs4149056 (T>C; V174A) variants on rosuvastatin discontinuation and LDL cholesterol changes in a multiethnic population in the United Arab Emirates (UAE). Methods In this multicenter prospective cohort study, 422 adults prescribed rosuvastatin were followed for 12 months. Discontinuation data were collected from records or phone calls. Genotyping was performed using TaqMan SNP assays. Cox regression and Kaplan-Meier analyses assessed discontinuation risk by genotype; LDL changes were analyzed using descriptive statistics and logistic regression. Results The ABCG2 rs2231142 T/T genotype had the highest risk of discontinuation (HR = 4.40, p < 0.001), followed by G/T (HR = 1.75). LDL change differed significantly between continuers (−17.86%) and discontinuers (+21.89%) (p < ...