Effect of genetic polymorphism of rosuvastatin transporter gene rs2231137 on its clinical efficacy and safety

Rosuvastatin is considered as the cornerstone therapy for primary and secondary prevention of cardiovascular diseases. Although clinical efficacy of rosuvastatin is well established, but wide inter-individual variations have been observed in its plasma levels, lipid lowering efficacy and adverse effects. So the current study was undertaken to evaluate the impact of genetic polymorphism of rosuvastatin efflux transporters on variable bioavailability, clinical efficacy and adverse effects. For this study, three hundred and eightyfour hyperlipidemic patients with low density lipoprotein more than 130 mg/dl and serum creatine phosphokinase level within normal range > 190 U/L were enrolled. Study design was quasi experimental and non-probability purposive sampling was done for recruitment of patients. It was conducted from June 2022 to December 2023 in two tertiary care hospitals of Pakistan. All the enrolled patients were treated with rosuvastatin (10 mg) once daily for 12 weeks. Fasting lipid profile, serum creatine phosphokinase, liver and renal function tests were measured at the start of study. After 12 weeks of intervention with rosuvastatin, biochemical tests, genotyping and plasma rosuvastatin levels were determined. Frequency of ABCG2 34 C > T polymorphism for wild type CC, heterozygous mutant CT and homozygous mutant TT genotypes were 55.2, 35.9 and 8.9% respectively. Patients with TT and CT have significantly higher plasma levels of rosuvastatin with mean value of 30.37 ± 6.4 ng/mL and 22.27 ± 4.68 ng/mL respectively as compared to CC genotypes 15.57 ± 8.94 ng/mL (p = < 0.001) which ultimately has improved lipid lowering efficacy. After 12 weeks of intervention, rosuvastatin significantly reduced total cholesterol (mean % decrease: CC 23.04 ± 10.05%, CT 37.43 ± 7.64%, TT 41.32 ± 6.97%, p = < 0.001), low density lipoprotein (mean % decrease: CC 31.11 ± 11.6% CT 47.27 ± 8.22% TT 53.29 ± 8.03%, p = < 0.001), very low density lipoprotein (mean% decrease: CC 36.23 ± 13.27%, CT 44.41 ± 10.29%, TT 54.5 ± 9.63%, p = < 0.001), triglycerides (mean% decrease: CC 24.34 ± 12.66%, TC 35.2 ± 10.47%, TT35.94 ± 8.6%, p = < 0.001) and high density lipoproteins (mean% increase: CC 9.19 ± 10.29%, CT 16.51 ± 9.33%, TT 23.10 ± 8.32%, p = < 0.001). Patients with TT and CT genotype has greater improvement in lipid profile compared with CC genotypes. Frequency of myopathy and hepatotoxicity in study population was 5.2 and 3.13% respectively. We conclude that rosuvastatin 10 mg is highly efficacious and well tolerated by most of the patients, however genotype profiling should be done before initiating rosuvastatin therapy to reduce the risk of adverse effects and to improve the compliance.