Genetics of high-density lipoproteins.
OBJECTIVE
High-density lipoproteins have multi-factorial anti-atherosclerosis properties: they have potent anti-oxidant effects and prevent the oxidation of low-density lipoproteins; they have anti-inflammatory effects; they modulate vascular endothelial cell function and transport cholesterol back to the liver for excretion into the bile - a process called reverse cholesterol transport. The present review focuses on genetic aspects of high-density lipoprotein metabolism, with genomic approaches used to identify genes that regulate high-density lipoproteins in humans.


RESULTS
Disorders of the many genes that code for proteins, including transporters, enzymes, receptors, transfer proteins and lipases, involved in high-density lipoprotein metabolism have been identified in humans as causing extremes of high-density lipoprotein cholesterol, and provide potential novel therapeutic avenues. These, however, explain fewer than 5% of the causes of low high-density lipoprotein cholesterol in the general population.


CONCLUSIONS
Genome-wide linkage studies of large cohorts, with discrete as well as quantitative trait loci analyses, followed by association studies have enabled the identification of large chromosomal regions that may harbor genes that modulate high-density lipoprotein cholesterol levels in humans. Using mouse genetics, the results of the HapMap project and novel genetic approaches will allow the discovery of novel genes in high-density lipoprotein metabolism.
Dastani
Zari
Z
Cardiovascular Genetics Laboratory, Division of Cardiology, McGill University Health Centre/Royal Victoria Hospital, Montréal, Québec, Canada.
Engert
James C
JC
Genest
Jacques
J
Marcil
Michel
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D050197:Atherosclerosis / Q000517:prevention & control*; D015331:Cohort Studies; D004591:Electrophoresis, Polyacrylamide Gel; D033141:Genetic Determinism; D008040:Genetic Linkage; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D040641:Quantitative Trait Loci
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL