Genetics of monogenic and complex dyslipidemias

Disorders of lipid metabolism, both monogenic and more genetically complex, are powerful risk factors for CHD. The major circulating lipids, cholesterol, phospholipids and triglycerides, are carried in the blood by several lipoprotein particles serving the physiological task of transporting dietary and endogenously produced lipids to peripheral tissues. The major pathways of lipoprotein metabolism in humans are illustrated in (Figure 24.1). Mutations in many of the lipoproteins, receptors and enzymes shown in the figure have been described in humans or engineered in rodents. Studies of these mutations have yielded the molecular basis of a wide range of dyslipidemias and in many cases elucidated the mechanism by which dysfunction of these proteins predispose to, or protect against, atherosclerosis and CHD.

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