Associations Between the Genotypes and Phenotype of CYP3A and the Lipid Response to Simvastatin in Chinese Patients with Hypercholesterolemia

Abstract

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.

Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new-onset diabetes in kidney transplant recipients

“…The potential clinical significance of PPARA SNPs (rs4253728 and rs4823613) has been reported recently in simvastatintreated patients: minor alleles, primarily related to reduced CYP3A4 activity, were associated with a larger reduction in total and LDL-cholesterol in response to simvastatin medication [13]. However, this effect of simvastatin was not observed in Chinese patients with hypercholesterolemia, in whom PPARA rs4823613 SNP was studied [14]. Similarly, PPARA rs4253728 SNP did not influence sirolimus metabolism in human liver microsomes, and was not associated with drug C 0 levels in kidney transplant patients [15].…”

No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia

“…Subsequently, Elens and colleagues have found a marginal association of CYP3A4*22 allele with greater reductions in TChol and LDLc in 80 simvastatin users [9]. However, the latter association was not replicated in a larger study of 273 simvastatin-treated Chinese patients [10], whereas the association of CYP3A4*22 allele with atorvastatin response has not been assessed so far. In the present study, we did not observe an association of CYP3A4*22 allele with statin dose titration or lipidlowering response either in the pooled sample or in the different statin treatments (atorvastatin or simvastatin).…”

“…Furthermore, in two different independent study cohorts, CYP3A4*22 allele was associated with response to simvastatin therapy in terms of dose titration to achieve optimal lipid control [8] and greater reduction in both total cholesterol (TChol) and LDLc [9]. However, the latter association could not be replicated in a more recent study in Chinese patients due to the absence of the CYP3A4*22 allele in the studied population [10]. The association of CYP3A4*22 allele with atorvastatin response has not been assessed so far.…”

Candidate‐Gene Study of Functional Polymorphisms inSLCO1B1andCYP3A4/5and the Cholesterol‐Lowering Response to Simvastatin

“…However, the percent reduction in LDL-C was not statistically different in CYP3A5 *3 homozygotes compared to CYP3A5 *1/*3 or CYP3A5 *1 homozygotes (31% vs. 46%, p = 0.083). No associations between CYP3A5 *3 and LDL-C lowering were detected in the following reports: Fiegenbaum et al ’s analysis of 99 Europeans that received 20 mg simvastatin daily for 6 months [23], Hu et al .’s analysis of 229 Chinese that received 40 mg simvastatin daily for 6 weeks [21], Bailey et al .’s analysis of 291 Europeans of the Genetic Effects On STATins (GEOSTAT-1) that received 40 mg simvastatin daily for 3 months [24] and Hopewell et al .’s analysis of 18,705 Europeans of the Heart Protection Study (HPS) that received 40 mg simvastatin daily for 4–6 weeks [15]. These findings collectively do not suggest that CYP3A5 *3 alters cholesterol-lowering response to simvastatin, at least not in the patient populations studied.…”