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Cholesterol, racial variation and targeted medicines

Nature Medicine volume 11, pages 122–123 (2005)Cite this article

One in 50 African-Americans have nonsense mutations in a gene that regulates cholesterol levels, PCSK9, accounting for a substantial lowering of blood LDL-cholesterol.

Only a year or so ago we thought we understood the primary determinants of low-density lipoprotein, 'bad' cholesterol in the bloodstream—apolipoprotein B and the LDL receptor. But since 2003, a flurry of human genetic studies have emphasized a new player, the gene encoding proprotein convertase subtilisin/kexin type 9, PCSK9. Abifadel and colleagues identified two missense mutations in PCSK9 to account for a form of autosomal dominant hypercholesterolemia in French families1. Soon thereafter, a third missense mutation was found in unrelated pedigrees in Utah and Norway2,3. Beyond monogenic disorders associated with the LDL receptor and apolipoprotein B, gain-of-function mutations in PCSK9 quickly emerged as the third cause of familial hypercholesterolemia.

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Figure 1: Schematic of PCSK9.

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  1. Cleveland Clinic Foundation and Cleveland Clinic Lerner Collge of Medicine, Case Western Reserve University, Cleveland, 44195, Ohio, USA

    Eric J Topol

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  1. Eric J Topol
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Topol, E. Cholesterol, racial variation and targeted medicines. Nat Med 11, 122–123 (2005). https://doi.org/10.1038/nm0205-122

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