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.