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Current clinical evidence on pioglitazone pharmacogenomics
Marina Kawaguchi-Suzuki1, Reginald F Frye
1Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida Gainesville, FL, USA.
Frontiers in Pharmacology
|December 11, 2013
Summary
Genetic variations in pioglitazone pathway genes influence drug response. The PPARG p.Pro12Ala polymorphism showed a favorable change in fasting blood glucose, suggesting pharmacogenomics can personalize pioglitazone therapy.
Area of Science:
- Pharmacogenomics
- Metabolic Diseases
- Drug Metabolism
Background:
- Pioglitazone, a thiazolidinedione, is an insulin-sensitizer approved for type 2 diabetes mellitus (T2DM).
- Its use is expanding due to pleiotropic effects beyond diabetes management.
- Variability in patient response necessitates understanding genetic influences.
Purpose of the Study:
- To summarize clinical evidence on pioglitazone pharmacogenomics.
- To examine how genetic variations affect pioglitazone pharmacokinetics and pharmacodynamics.
- To test the hypothesis that genetic variation in PPARG associates with pioglitazone response variability.
Main Methods:
- Review of current clinical evidence on pioglitazone pharmacogenomics.
- Examination of genetic variations impacting drug metabolism and effects.
- Meta-analysis of the PPARG p.Pro12Ala polymorphism and pioglitazone response.
Main Results:
- CYP2C8 and PPARG gene polymorphisms are most studied, influencing pioglitazone pharmacokinetics and pharmacodynamics.
- PPARG p.Pro12Ala carriers showed a more favorable change in fasting blood glucose compared to wild-type.
- Replication in independent cohorts is needed for many gene associations; biological functionality remains unknown.
Conclusions:
- Genetic variations in pioglitazone pathway genes contribute to observed drug response variability.
- The PPARG p.Pro12Ala polymorphism is associated with improved glycemic control.
- Pharmacogenomics offers a potential tool for individualizing pioglitazone therapy in T2DM and other conditions.
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