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
  • 1. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. [email protected]
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.