Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin

Genovefa Kolovou 1, *, Georgia Ragia 2, Vana Kolovou 1, 3, Constantinos Mihas 4, Niki Katsiki 5, Ioannis Vasiliadis 1, Sophie Mavrogeni 1, Vassiliki Vartela 1, Anna Tavridou 1, Vangelis G. Manolopoulos 2
1 Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
2 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
3 Molecular Immunology Laboratory, Onassis Cardiac Surgery Center Athens, Greece;
4 Internal Medicine Department, Kimi General Hospital, Kimi, Greece;
5 Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece

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© Kolovou et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Onassis Cardiac Surgery Center, 356 Sygrou Ave 176 74 Athens, Greece; Tel: +30 210 9493520; Fax: +30 210 9493336; E-mail:


Background: One of the promises of human genetics is individualized therapy. Therefore, we evaluated the impact of CYP3A5 gene polymorphism on the effectiveness of simvastatin (a HMG-CoA reductase inhibitor). Methods: Patients (n = 191) with hypercholesterolemia were treated with simvastatin for at least 6 months and were genotyped for the CYP3A5 polymorphism. Results: The frequency of CYP3A5 polymorphism was 0.5% for WT (wild-type), 15.6% for HT (heterozygous, expressors) and 83.9% for HM (homozygous, non-expressors). Differences in lipid profile before and after dose-response of simvastatin treatment were described as % difference {[(variable after-variable before)/variable before]*100}. There was a trend towards the decrease of low density lipoprotein cholesterol (LDL-C) in HT individuals who had a -35.2% reduction with a dose of 20 mg simvastatin and HM individuals who had a slightly higher decrease (-37.5%) despite the lower dose of simvastatin (10 mg, p = 0.07). Furthermore, HT genotype individuals had significantly higher than expected (6-8%) LDL-C % difference between 20 and 40 mg of simvastatin (-35.2 vs -49.2%, p = 0.037). In individuals with HM genotype a significant LDL-C % difference was found between 10 and 40 mg of simvastatin (-37.5 vs -48.4%, p = 0.023). Conclusion: The individuals with HM polymorphism display a trend towards higher LDL-C reductions compared with HT polymorphism. Within the same genotype, differences between doses were also observed. These findings need to be confirmed in larger studies.

Keywords: Simvastatin, CYP3A5 gene polymorphism, low density lipoprotein cholesterol..