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CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control

CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control Abstract Background: Statins are indicated for prevention of atherosclerotic cardiovascular disease. Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. CYP3A4/5 combined genotype approaches have proved useful in some studies involving CYP3A substrates. We intend to compare a combined genotype analysis to our previously reported single gene CYP3A4 analysis. Methods: A total of 235 patients receiving stable statin doses were genotyped and grouped by CYP3A4/5 status. Results: The number and demographic composition of the patients categorized into the combined genotype groups were consistent with those reported for other cohorts. Dose requirement was significantly associated with the ordered combined-genotype grouping; median daily doses were nearly 40% greater for CYP3A4/5 intermediate metabolizers compared with poor metabolizers, and median daily doses were nearly double for extensive metabolizers compared with poor metabolizers. The combined-genotype approach, however, did not improve the genotype-dosage correlation p-values when compared with the previously-reported analysis; values changed from 0.129 to 0.166, 0.036 to 0.185, and 0.014 to 0.044 for atorvastatin, simvastatin, and the combined statin analysis, respectively. Conclusions: The previously-reported single-gene approach was superior for predicting statin dose requirement in this cohort. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Drug Interactions de Gruyter

CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control

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Publisher
de Gruyter
Copyright
Copyright © 2013 by the
ISSN
0792-5077
eISSN
2191-0162
DOI
10.1515/dmdi-2012-0031
pmid
23314529
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: Statins are indicated for prevention of atherosclerotic cardiovascular disease. Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. CYP3A4/5 combined genotype approaches have proved useful in some studies involving CYP3A substrates. We intend to compare a combined genotype analysis to our previously reported single gene CYP3A4 analysis. Methods: A total of 235 patients receiving stable statin doses were genotyped and grouped by CYP3A4/5 status. Results: The number and demographic composition of the patients categorized into the combined genotype groups were consistent with those reported for other cohorts. Dose requirement was significantly associated with the ordered combined-genotype grouping; median daily doses were nearly 40% greater for CYP3A4/5 intermediate metabolizers compared with poor metabolizers, and median daily doses were nearly double for extensive metabolizers compared with poor metabolizers. The combined-genotype approach, however, did not improve the genotype-dosage correlation p-values when compared with the previously-reported analysis; values changed from 0.129 to 0.166, 0.036 to 0.185, and 0.014 to 0.044 for atorvastatin, simvastatin, and the combined statin analysis, respectively. Conclusions: The previously-reported single-gene approach was superior for predicting statin dose requirement in this cohort.

Journal

Drug Metabolism and Drug Interactions – de Gruyter

Published: Feb 1, 2013

References

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    Wang
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    Shin
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    Kivisto
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    Xie
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    Wilke
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    Park
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    Park
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    Elens
  • van de Effect of a new functional polymorphism on calcineurin inhibitors dose requirements and trough blood levels in stable renal transplant patients
    Elens
  • Genetic variability in its possible consequences
    Xie
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    Elens
  • Association Alert cardiovascular disease costs Available at http www americanheart org Accessed