Genetics of Dyslipidemia

2.2.12- Hepatic Lipase, a lipase for lipoprotein remodeling.- 2.2.13- Other Lipases.- 2.2.2- Apolipoproteins.- 2.2.21- Apolipoprotein C-II, an activator of lipoprotein lipase.- 2.2.22- Apoliprotein C-I, a modulator of lipoprotein catabolism.- 2.2.23- Apolipoprotein E, the major apolipoprotein for intermediate lipoproteins.- 2.2.3- Receptors.- 2.2.31- LRP, a multifunctional receptor for intermediate lipoproteins.- 2.2.32- Megalin, an ancient member of the LDL receptor gene family expressed in the kidney.- 2.2.33- VLDL Receptor (LR8), a multifunctional receptor with species-dependent requirements.- 2.3- Genes of the Reverse Pathway of lipoprotein metabolism.- 2.3.1- Apolipoproteins.- 2.3.11- Apolipoprotein A-I, a major component of HDL.- 2.3.12- Apoliprotein C-III, a modulator for triglyceride-rich lipoprotein catabolism.- 2.3.13- Apolipoprotein A-IV, a component of intestinal lipoproteins.- 2.3.14- Apolipoprotein A-II, a modulator of HDL metabolism.- 2.3.2- Circulating Enzymes and Transfer Proteins for Lipoprotein Remodeling.- 2.3.21- Lecithin Cholesterol Acyl transferase (LCAT), a rate limiting enzyme for HDL metabolism.- 2.3.22- Cholesteryl Ester Transfer Protein (CETP), a « points man» of lipoprotein metabolism.- 2.3.23- Phospholipid Transfer Protein (PLTP), a major component of HDL formation in plasma.- 2.3.3- Receptors.- 2.3.31- ABC-1, or cholesterol efflux regulatory protein, a gene for Tangier Disease and Familial hypoalphalipoproteinemia.- 2.3.32- Scavenger Receptor class B-1 (SR-BI), a multifunctional receptor for the selective uptake of cholesterol.- 2.3.33- Cubilin, a receptor for HDL in the kidney.- 2.4- Other Regulatory Pathways of Lipoprotein Metabolism.- 2.4.1- The Traffic of Intracellular Lipids.- 2.4.11- Lipid tafficking in cellular compartments.- + Niemann Pick Disease type C.- + Lysosomal Acid Lipase.- + Acyl-CoA: Cholesterol acyl transferases (ACAT).- + Intracellular fatty acid trafficking.- 2.4.12- Nuclear coordinators of intracellular energy resources.- + SREBPs (Sterol Responsive Element Binding Proteins).- + PPARs (Peroxisome Proliferator Activated Receptors).- + LXR (Liver X Receptor), FXR (Farnesoid X Receptor).- + Lamins A/C.- 2.4.2- The Biosynthesis of Bile Acids.- 2.4.3- Other Apolipoproteins.- 2.4.4- Anti-toxic and Anti-oxidative Protection.- III- The Genetic Basis of Dyslipidemias.- 3.1- The Genetic Architecture of Lipoprotein Metabolism.- 3.1.1- The functionality of candidate genes.- 3.1.11- Levels of functional significance of candidate genes.- 3.1.12- The redundancy of candidate genes.- 3.1.13- The multifunctionality of candidate genes.- 3.1.2- The driving forces of lipoprotein metabolism.- 3.2- The Candidate Gene Approach.- 3.2.1- In human disorders of lipoprotein metabolism.- 3.2.11- Identifying the disease causing mutation in inherited dyslipidemia.- 3.2.12- A redefinition of inherited dyslipidemia.- 3.2.13- The evidence of genetic interactions.- 3.2.14- Identifying risk alleles for complex diseases in populations.- 3.2.15- Genetic determinants of dyslipidemia in populations.- 3.2.2- The candidate gene approach in experimental models of dyslipidemia.- 3.2.21- In vitro studies and cell cultures.- 3.2.22- In vivo studies and animal models.- 3.2.3- Clinical issues of the candidate gene approach.- 3.2.31- Applications in current clinical care.- 3.2.32- Corrective gene therapy.- 3.2.4- Present limitations to the candidate gene approach.- 3.3- Novel Genes, Novel Approaches.- 3.3.1- Identifying novel genes of lipoprotein metabolism.- 3.3.11- Positional cloning of novel genes.- 3.3.12- Expression cloning of novel genes.- 3.3.13- In silico cloning of novel genes.- 3.3.2- Novel approaches to identify novel mechanisms of human dyslipidemia.- Conclusion.- References.