A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

Toni I. Pollin, Coleen M. Damcott, Haiqing Shen, Sandra H. Ott, John Shelton, Richard B. Horenstein, Wendy Post, John C. McLenithan, Lawrence F. Bielak, Patricia A. Peyser, Braxton D. Mitchell, Michael Miller, Jeffrey R. O'Connell, Alan R. Shuldiner

Research output: Contribution to journalArticle

Abstract

Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.

Original languageEnglish (US)
Pages (from-to)1702-1705
Number of pages4
JournalScience
Volume322
Issue number5908
DOIs
StatePublished - Dec 12 2008

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection'. Together they form a unique fingerprint.

  • Cite this

    Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., Mitchell, B. D., Miller, M., O'Connell, J. R., & Shuldiner, A. R. (2008). A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science, 322(5908), 1702-1705. https://doi.org/10.1126/science.1161524