The lipid-lowering efficacy of rosuvastatin is associated with variations in SLCO1B1: a 12-month prospective cohort study.

Abstract

Statins' efficacy and safety are subject to wide inter-individual variability, partly due to genetic predisposition. Studies have shown that the genetic variations in the common solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene polymorphisms affect the transport of statins' transport into hepatocytes, their plasma concentration, and circulation time. The ultimate result is variable and personalized statins response and statin-associated muscular symptoms (SAMS). Here we report an update on the differential response to rosuvastatin therapy in the Pakistani population. A total of 166 hyperlipidemic patients on rosuvastatin were prospectively followed for 24 weeks. Muscle symptoms were recorded after 6-8 weeks of therapy, and assessment was done according to the SAMS-clinical index tool. Patients were genotyped for SLCO1B1 c.521T>C and c.388A>G polymorphisms, for association with lipid-lowering response and statin-associated muscle symptoms. The plasma level of rosuvastatin was determined through Liquid chromatography-mass spectrometry (LCMS) for possible correlation with adverse effects and lipid-lowering efficacy. Mean reduction in low-density lipoprotein cholesterol (LDL-C) was 42.34 mg/dl (p<0.001), 35.66 mg/dl (p<0.001), and 24.47 mg/dl (p=0.202) in reference, heterozygous and mutant homozygous groups of SLCO1B1 c.521T>C, respectively. A 15.70% and 42.14% diminished LDL-C reduction was observed in c.521TC and c.521CC, respectively, compared to the reference c.521TT genotype. Similarly, for SLCO1B1 c.388A>G, 20.50% and 29.40% less LDL-C lowering effect was observed in heterozygous and mutant homozygous carriers, respectively. SAMS were observed in 37% and 33% of heterozygous and minor homozygous, respectively, (p=0.059). The rosuvastatin plasma level was 1.89-fold higher in the c.521CC genotype than in the reference homozygous type. Differential lipid-lowering response and muscular symptoms due to rosuvastatin are associated with the SLCO1B1 common polymorphisms. Further studies are needed to validate dose adjustment and rationalization.