2. Academic Validation
  3. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

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

  • Science. 2008 Dec 12;322(5908):1702-5. doi: 10.1126/science.1161524.
Toni I Pollin 1,  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
Affiliations

Affiliation

  • 1 Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. tpollin@medicine.umaryland.edu
PMID: 19074352 DOI: 10.1126/science.1161524
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.

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