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Fenofibrate and metabolic syndrome
Aldi T Kraja1, Michael A Province, Robert J Straka
1Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Ave., Campus Box 8506, St. Louis, MO 63110, USA. aldi@wustl.edu
Endocrine, Metabolic & Immune Disorders Drug Targets
|April 22, 2010
Summary
Fenofibrate effectively manages dyslipidemia, particularly for metabolic syndrome patients. Genetic factors influence individual responses, necessitating further research to identify optimal patient candidates for fenofibrate therapy.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Metabolic Disorders
Background:
- Fenofibrate (FF) is a fibric acid derivative used since 1998 to treat dyslipidemia.
- FF effectively reduces triglycerides and LDL cholesterol while increasing HDL cholesterol.
- Its mechanism involves PPAR-alpha agonism, but genetic influences on response variability are not fully understood.
Purpose of the Study:
- To review the literature on fenofibrate's use in dyslipidemia management.
- To explore the genetic determinants of individual responses to fenofibrate treatment.
- To identify patient subgroups who benefit most from fenofibrate therapy.
Main Methods:
- Review of clinical trials and genetic association studies.
- Analysis of data from the GOLDN study identifying SNPs associated with lipid levels and FF response.
- Examination of fenofibrate's mechanism of action and gene transcription alterations.
Main Results:
- Fenofibrate demonstrates significant reductions in triglycerides and LDL-C, and increases in HDL-C.
- Genetic variations in genes like APOA5, APOC3, APOA4, PPARA, and LPL are associated with lipid levels and response to FF.
- Specific SNPs (e.g., NOS3-rs1799983) appear to modulate the overall response to fenofibrate treatment.
Conclusions:
- Fenofibrate is beneficial for dyslipidemia, especially in patients with metabolic syndrome.
- Understanding genetic variability is crucial for optimizing fenofibrate therapy.
- Further research is needed to pinpoint individuals who will achieve clinical benefits from fenofibrate, particularly those with type 2 diabetes.
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