Pharmacogenomic analysis of low-density lipoprotein receptor 3' untranslated region genetic variants influencing rosuvastatin efficacy in Chinese dyslipidemia patients.

Objectives: Dyslipidemia is a crucial risk factor for atherosclerotic cardiovascular disease. Although rosuvastatin is widely used, treatment response varies significantly due to genetic variation. This study investigated the pharmacogenomic impact of low-density lipoprotein receptor (LDLR) 3' untranslated region (UTR) variants on rosuvastatin efficacy in a Chinese Han adult cohort with dyslipidemia.

Methods: A cohort of 113 Chinese participants receiving 10 mg rosuvastatin daily was sequenced for LDLR 3'UTR variants. Haploview was used to assess linkage disequilibrium (LD) patterns and haplotype structures. Multivariate regression modeling was employed to assess the influence of genetic variants on therapeutic outcomes.

Results: Seventeen LDLR 3'UTR variants were identified. A crosspopulation comparative assessment revealed significant variation in allele frequencies across distinct ethnic groups. Five variants (rs14158, rs2738466, rs5742911, rs17249057, and rs17249064) were in complete LD ( D ' = 1 and r2  = 1). CHANGE analysis revealed that rosuvastatin efficacy was significantly influenced by rs2738465, rs55903358, rs186461273, and rs751672818, while ANCOVA indicated that baseline triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and patient age, alongside rs2738467, rs143587805, and rs751672818 significantly impacted treatment response. Given the bias correction properties and well-established efficiency, results derived from ANCOVA were preferred. These findings were first reported, highlighting LDLR variants can be used as predictive markers for precision medicine for rosuvastatin in the Chinese population.

Conclusions: These findings highlight the role of LDLR 3'UTR as a critical pharmacogenomic locus. Our results advance understanding of genetic predictors for personalized statin therapy.