CYP3A5 genotyping for assessing the efficacy of treatment with simvastatin and atorvastatin.
In this work, we examined the impact of polymorphism in the cytochrome P450 (CYP) 3A5 gene, CYP3A5*1 (6986A > G, rs 776746), on the reduction in the lipid levels caused by simvastatin and atorvastatin. We studied 350 hyperlipidemic patients who received 10-40 mg of atorvastatin (n = 175) or simvastatin (n = 175) daily. Genotyping for CYP3A5 was done by PCR-RFLP analysis. Differences in the lipid profile before and after treatment were expressed as the % difference. The frequency of CYP3A5polymorphism was 13.4% for heterozygotes and 86.6% for homozygotes. Comparison of the responses to same dose of each drug showed that the highest % difference was associated with total cholesterol (TC) in subjects receiving atorvastatin 40 mg compared with simvastatin 40 mg (p = 0.048). However, comparison of the responses to equivalent doses of atorvastatin vs. simvastatin revealed no difference in the % change in any of the lipid parameters examined. In individuals with the same CYP3A5 genotype, a head to head comparison of the efficacy of the same dose of simvastatin vs. atorvastatin revealed an advantage for atorvastatin. For equivalent doses of atorvastatin vs. simvastatin there was no difference in the % change in any of the lipid parameters examined. Within the same genotype there was a significant difference in the % change related to the drug treatment.
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Genovefa
G
Kolovou
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece ; Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece.
Vana
V
Kolovou
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Georgia
G
Ragia
Department of Internal Medicine, Kimi General Hospital, Kimi, Greece.
Constantinos
C
Mihas
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Olga
O
Diakoumakou
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Ioannis
I
Vasiliadis
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Sophie
S
Mavrogeni
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Vassiliki
V
Vartela
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Vangelis G
VG
Manolopoulos
CYP3A5 gene polymorphism; atorvastatin; cholesterol; simvastatin