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Recent developments in the genetics of LDL deficiency

Hooper, Amanda J.a,b; Burnett, John R.a,b

Current Opinion in Lipidology: April 2013 - Volume 24 - Issue 2 - p 111–115
doi: 10.1097/MOL.0b013e32835ca0d9

Purpose of review: Inherited diseases of lipoprotein metabolism may give rise to marked hypocholesterolemia with low or absent levels of LDL, depending on the gene involved and mode of inheritance of the condition, together with the severity of the mutation or mutations present. In this review, we discuss the recent developments in the genetics of LDL deficiency.

Recent findings: Carriers of a single loss-of-function variant in ANGPTL3 have reduced LDL-cholesterol and triglyceride concentrations, whereas homozygotes have markedly reduced LDL-cholesterol, triglyceride and HDL-cholesterol concentrations, a recessive form of hypocholesterolemia designated as familial combined hypolipidemia.

Summary: The identification of loss-of-function ANGPTL3 mutations as a cause of familial combined hypolipidemia suggests a new mechanism for the regulation of LDL metabolism in humans, thereby making ANGPTL3 an attractive protein to target for therapeutics.

aDepartment of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital

bSchools of Medicine and Pharmacology and Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia

Correspondence to John R. Burnett, Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, GPO Box X2213, Perth WA, Australia. 6847. Tel: +61 8 9224 3121; fax: +61 8 9224 1789; e-mail:

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins