The impact of the ABCG2 421C>A polymorphism on the disposition of the statins varies between different drugs and the effect on systemic exposure was greater in the case of rosuvastatin than other statins. This genetic variant was associated with greater low-density lipoprotein cholesterol response to rosuvastatin in Chinese and caucasian patients. The effect of the ABCG2 421C>A polymorphism on the lipid response to other substrate statins and clinical outcomes need to be evaluated in future studies.

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.

The results of this study suggest that genetic polymorphisms in CYP3A or other regulatory genes, or the CYP3A activity itself, is unlikely to have a significant effect on the lipid-lowering responses to simvastatin in Chinese patients.