Dataset Information

Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.

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.

SUBMITTER: Kolovou G

PROVIDER: S-EPMC3959175 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.

Kolovou Genovefa G Ragia Georgia G Kolovou Vana V Mihas Constantinos C Katsiki Niki N Vasiliadis Ioannis I Mavrogeni Sophie S Vartela Vassiliki V Tavridou Anna A Manolopoulos Vangelis G VG

The open cardiovascular medicine journal 20140207

<h4>Background</h4>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).<h4>Methods</h4>Patients (n = 191) with hypercholesterolemia were treated with simvastatin for at least 6 months and were genotyped for the CYP3A5 polymorphism.<h4>Results</h4>The frequency of CYP3A5 polymorphism was 0.5% for WT (wild-type), 15.6% for HT (heterozygous, expressors) and ...[more]

PMID: 24653785

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Dataset Information

Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.

Background

Methods

Results

Conclusion

Publications

Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.

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