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Regulatory Gene Mutations Affecting Apolipoprotein Gene Expression: Functions and Regulatory Behavior of Known Genes May Guide Future Pharmacogenomic Approaches to Therapy
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Vassilis I. Zannis
Veröffentlicht/Copyright:
1. Juni 2005
Abstract
A pharmacogenomic approach to therapy requires systematic knowledge of the regulatory regions of the genes, as well as basic understanding of transcriptional regulatory mechanisms of genes. Using the apolipoprotein (apo) A-I/CIII gene cluster as a model system, we have identified by in vitro and in vivo studies the regulatory elements and the factors which control its transcription. Studies in transgenic mice established that the hepatocyte nuclear factor (HNF-4) binding site of the apoCIII enhancer, which controls transcription of both genes, is required for the intestinal expression of apoA-I and apoCIII genes, and enhances synergistically their hepatic transcription in vivo. The three Sp1 sites of the enhancer are also required for the intestinal expression of apoA-I and apoCIII genes in vivo, and for the enhancement of the hepatic transcription. The regulation of the apoE/apoCI/apoCIV/apoCII cluster is also cited. It is expected that identification of the regulatory regions of genes will be soon accelerated by the sequencing of several mammalian genomes. The functional analyses of the regulatory domains of genes involved in lipid homeostasis, combined with cross-species sequence comparisons in the near future, may identify natural regulatory gene polymorphisms in the general population that will permit rational pharmacogenomic approaches for treatment of dyslipidemias.
:
Published Online: 2005-06-01
Published in Print: 2003-04-25
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- First Santorini Conference: From Genetic Variations to Risk Prediction and Pharmacogenomics
- Pharmacogenetics and Pharmacogenomics in Drug Discovery and Development: An Overview
- Regulatory Gene Mutations Affecting Apolipoprotein Gene Expression: Functions and Regulatory Behavior of Known Genes May Guide Future Pharmacogenomic Approaches to Therapy
- The Proteome: Anno Domini 2002
- Cardiac Sodium Channel Diseases
- Haemophilia B: From Molecular Diagnosis to Gene Therapy
- The Use of Denaturing High-Performance Liquid Chromatography (DHPLC) for the Analysis of Genetic Variations: Impact for Diagnostics and Pharmacogenetics
- Molecular Diagnostics by Microelectronic Microchips
- Molecular Beacons as Diagnostic Tools: Technology and Applications
- Electrochemical DNA Sensor for Detection of Single Nucleotide Polymorphisms
- Comparison of Standard PCR and the LightCycler® Technique to Determine the Thrombophilic Mutations: An Efficiency and Cost Study
- Impact of Purified Water Quality on Molecular Biology Experiments
- Which Are the best Tools for Specific Clinical Application (Chips, Multiplex, Mass Spec Profile, etc.)?
- Genetic Variations Observed in Arterial and Venous Thromboembolism – Relevance for Therapy, Risk Prevention and Prognosis
- The TNF- α Gene NcoI Polymorphism at Position –308 of the Promoter Influences Insulin Resistance, and Increases Serum Triglycerides after Postprandial Lipaemia in Familiar Obesity
- The –308 G/A Tumor Necrosis Factor-α Gene Dimorphism: A Risk Factor for Unstable Angina
- The Apolipoprotein AV Gene and Diurnal Triglyceridaemia in Normolipidaemic Subjects
- Left Ventricular Size, Mass and Function in Relation to Angiotensin-Converting Enzyme Gene and Angiotensin-II Type 1 Receptor Gene Polymorphisms in Patients with Coronary Artery Disease
- Analysis of Multiple Single Nucleotide Polymorphisms of Candidate Genes Related to Coronary Heart Disease Susceptibility by Using Support Vector Machines
- PON1-192 Phenotype and Genotype Assessments in 918 Subjects of the Stanislas Cohort Study
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- Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism and the B-Vitamins: A Facet of Nature-Nurture Interplay
- Which, and How Limited Number of Polymorphisms Should Be Selected per Disease, Risk Assessment, Health Profile or Biological System?
- Ethical Issues: Should We Give the Predictive Genetic Profile to the Citizens?
- Pharmacogenetics and Responders to a Therapy: Theoretical Background and Practical Problems
- Pharmacogenetics of Drug Metabolising Enzymes: Importance for Personalised Medicine
- Pharmacogenomics and Pharmacogenetics of Cholesterol-Lowering Therapy
- Pharmacogenomics of Drugs Affecting the Cardiovascular System
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