Alqasrawi Mais N, Al-Mahayri Zeina N, Khasawneh Lubna Q, AlBawa'neh Areej S, Dabaghie Lilas, Altoum Sahar M, Hamza Dana, Aburuz Salahdein, Misra Virendra, Jamil Gohar, Ouda Husam, Al-Bakshy Faiz, AlAhamad Khuzama, Al-Ahmad Mohammad M, Al-Maskari Fatima, AlKaabi Juma, Patrinos George P, Ali Bassam R
Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates.
Front Pharmacol. 2025 Aug 29;16:1656520. doi: 10.3389/fphar.2025.1656520. eCollection 2025.
Rosuvastatin is widely used for cardiovascular risk reduction, but treatment discontinuation limits its long-term benefit. Genetic variants, particularly in and , influence rosuvastatin's transport, efficacy, and tolerability. The 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 rs2231142 (G>T; Q141K) and rs4149056 (T>C; V174A) variants on rosuvastatin discontinuation and LDL cholesterol changes in a multiethnic population in the United Arab Emirates (UAE).
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.
The 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 < 0.001). The variant was more frequent among discontinuers (30.6% vs. 17.4%, p = 0.0026). rs4149056 was not associated with discontinuation.
Minor allele carriers are at higher risk of discontinuation due to adverse effects. Genetic testing for may support personalized rosuvastatin therapy and improve adherence.
瑞舒伐他汀被广泛用于降低心血管疾病风险，但治疗中断限制了其长期益处。基因变异，尤其是在[基因名称1]和[基因名称2]中的变异，会影响瑞舒伐他汀的转运、疗效和耐受性。rs2231142变异与全身暴露增加导致的疗效增强有关；然而，它也增加了不良反应的风险，尤其是与肌肉相关的症状。在真实世界的多民族人群中评估这些变异的影响对于提高依从性和指导个性化治疗至关重要。本研究的目的是调查rs2231142（G>T；Q141K）和[基因名称2] rs4149056（T>C；V174A）变异对阿拉伯联合酋长国（UAE）多民族人群中瑞舒伐他汀停药和低密度脂蛋白胆固醇变化的影响。
在这项多中心前瞻性队列研究中，对422名开具瑞舒伐他汀处方的成年人进行了12个月的随访。从记录或电话中收集停药数据。使用TaqMan SNP分析进行基因分型。Cox回归和Kaplan-Meier分析按基因型评估停药风险；使用描述性统计和逻辑回归分析低密度脂蛋白变化。
rs2231142 T/T基因型的停药风险最高（HR = 4.40，p < （此处原文似乎有误，推测可能是p < 0.001）），其次是G/T（HR = 1.75）。继续用药者（-17.86%）和停药者（+21.89%）之间的低密度脂蛋白变化有显著差异（p < 0.001）。[基因名称2]变异在停药者中更常见（30.6%对17.4%，p = 0.0026）。rs4149056与停药无关。
次要等位基因携带者因不良反应而停药的风险更高。[基因名称2]的基因检测可能支持瑞舒伐他汀的个性化治疗并提高依从性。
