The ATP-binding cassette G2 (ABCG2) c.421C>A (rs2231142) polymorphism influences the pharmacokinetics of rosuvastatin. We examined whether this polymorphism influences the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of the drug. In 305 Chinese patients with hypercholesterolemia who were treated with rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be significantly associated with greater reduction in LDL-C level, in a gene-dose-dependent manner. As compared with subjects with the c.421CC genotype, those with the c.421AA genotype showed a 6.9% greater reduction in LDL-C level, which would be equivalent to the effect obtained by doubling the dose of rosuvastatin.

These findings suggest that the increased plasma concentrations of rosuvastatin in Chinese patients are associated with increased lipid-lowering effects and lower doses of rosuvastatin should be effective in subjects with the ABCG2 421C>A variant.

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Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.