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From CHD Susceptibility Genes to New Therapeutics

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The identification of genetic disease susceptibility genes has been pursued with the expectation to rapidly translate causal disease mechanisms into innovative therapeutics. Indeed, several susceptibility genes have led to the elucidation of molecular pathologies and the development of new drugs and diagnostics for disease management. We review in this article how the identification of susceptibility genes for high density lipoprotein (HDL) particle deficiencies have changed our understanding of lipid metabolism and how this understanding is being used in translational research for the discovery of new treatment strategies.

The identification of ATP-binding cassette transporter A1 (ABCA1) and transcriptional repressor zinc finger protein 202 (ZNF202) as susceptibility genes for coronary heart disease (CHD) and hypoalphalipoproteinemia, led to the characterization of a functional network of genes involved in lipid metabolism.

Currently available drug classes for metabolic and dyslipidemic indications such as the glitazones, fibrates and statins have been shown to modulate the expression of some components involved in reverse cholesterol transport. The characterization of new regulators of this gene network that are amenable to pharmaceutical modulation such as the nuclear receptors FXR, LXR, PXR, PPAR and RXR may offer new perspectives in disease treatment, if undesirable side effects can be diminished. In addition, the characterization of ABCA1-mediated lipid efflux systems has provided new biomarkers to assess the pharmacological effects of new therapeutic strategies on reverse cholesterol transport.

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Keywords: atp-binding cassette transporter a1; chd susceptibility genes; coronary heart disease; hypoalphalipoproteinemia; transcriptional repressor zinc finger

Document Type: Review Article

Publication date: June 1, 2003

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  • Current Pharmacogenomics provides comprehensive overviews of all current research on pharmacogenomics and pharmacogenetics. All areas of the field from pre-clinical to clinical research are covered, including related areas such as genomics, proteomics, target discovery, bioinformatics and novel diagnostics. This international journal is peer-reviewed and publishes both mini- and full review articles.

    The journal has become essential reading for all researchers and clinicians with interests in pharmacogenomics and pharmacogenetics.
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