Minority Health Archive

Cholesterol, racial variation and targeted medicines

Topol, Eric J (2005) Cholesterol, racial variation and targeted medicines. Nature Medicine, 11 (2). pp. 122-123.

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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. Cohen et al. have now taken the genetics of PCSK9 further4. Using the Dallas Heart Study cohort of 3,553 multiethnic patients, they genoomically screened 128 individuals who had markedly reduced choleesterol levels. Although almost all previous studies have focused on high levels of LDL cholesterol tied to coronary artery disease, this was a clever way to further probe PCSK9 protein's potential impact on blood LDL cholesterol levels. Two nonsense, loss-of-function PCSK9 mutations were identified, occurring in 2% of African Americans and less than 0.1% of European Americans and Hispanics. Both mutations introduce a stop codon and are predicted to result in a truncated protein.

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Item Type: Article
Uncontrolled Keywords: LDL-cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), African American, European American, Hispanic, genetics
Subjects: Health > Pharmacotherapy
Research > studies
Research > Genetics and Race
Related URLs:
    Depositing User: Kismet Loftin-Bell
    Date Deposited: 17 Aug 2005
    Last Modified: 09 Jun 2011 10:53
    Link to this item (URI): http://health-equity.lib.umd.edu/id/eprint/200

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