Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.
Open Cardiovasc Med J
; 8: 12-7, 2014.
Article
in En
| MEDLINE
| ID: mdl-24653785
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Open Cardiovasc Med J
Year:
2014
Document type:
Article