Genetic Determinants of HDL Metabolism
A. Ossoli, M. Gomaraschi, G. Franceschini and L. Calabresi
Affiliation: Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Via Balzaretti 9, 20133 Milano, Italy.
Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of lipoprotein particles, with
subclasses that can be separated and identified according to density, size, surface charge as well as shape and protein
composition. There is evidence that these subclasses may differ in their functional properties. The individual plasma HDL
cholesterol (HDL-C) level is generally taken as a snapshot of the steady-state concentration of all circulating HDL subclasses
together, but this is insufficient to capture the structural and functional variation in HDL particles. HDL are continuously
remodeled and metabolized in plasma and interstitial fluids, through the interaction with a large number of factors,
including structural proteins, membrane transporters, enzymes, transfer proteins and receptors. Genetic variation in
these factors can lead to essential changes in plasma HDL levels, and to remarkable changes in HDL particle density, size,
surface charge, shape, and composition in lipids and apolipoproteins. This review discusses the impact of rare mutations
and common variants in genes encoding factors involved in HDL remodeling and metabolism on plasma HDL-C levels
and particle distribution. The study of the effects of human genetic variation in major players in HDL metabolism provides
important clues on how individual factors modulate the formation, maturation, remodeling and catabolism of HDL.
Keywords: ABC transporters, cholesteryl ester transfer protein, high density lipoproteins, lecithin: cholesterol acyltransferase.
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