Abstract
Purpose
Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins.
Methods
We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day-1 p.o.) for 4 weeks. Genotyping of CYP3A4*1G was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment by enzymatic assays.
Results
The frequency of CYP3A4*1G in Chinese hyperlipidemic patients was 0.276. After atorvastatin treatment, the mean percentage reduction in serum TC was 16.8 ± 3.3% (*1/*1), 17.8 ± 3.8% (*1/*1G), and 20.9 ± 5.0% (*1G/*1G), respectively. The CYP3A4*1G polymorphism had a gene-dose-dependent effect on percentage reduction in serum TC (P < 0.01). Conversely, there was no significant association between lipid-lowering efficacy of simvastatin and CYP3A4*1G polymorphism.
Conclusions
Carrying CYP3A4*1G increase the lipid-lowering efficacy of atorvastatin and may have no significant effect on simvastatin treatment.
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Acknowledgements
This work was supported by grants from the Science Foundation for Distinguished Young Scholars of Henan Province (No. 074100510020) and the Engineering Project for Innovative Scholars of Henan Province (No. 2004020). The work was completed in the Henan key laboratory of molecular medicine. P.R. China. We thank Prof. Hu Dong-sheng (Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China) for helping us analyze data.
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Gao, Y., Zhang, Lr. & Fu, Q. CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin. Eur J Clin Pharmacol 64, 877–882 (2008). https://doi.org/10.1007/s00228-008-0502-x
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DOI: https://doi.org/10.1007/s00228-008-0502-x