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

BACKGROUND

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).

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 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.

CONCLUSION

Minor allele carriers are at higher risk of discontinuation due to adverse effects. Genetic testing for may support personalized rosuvastatin therapy and improve adherence.