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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoprotein C-III / blood
  • Apolipoprotein C-III / genetics*
  • Cholesterol / blood
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Christianity
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / prevention & control*
  • Dietary Fats / administration & dosage
  • Fasting
  • Female
  • Genome-Wide Association Study
  • Haplotypes
  • Heterozygote
  • Humans
  • Linkage Disequilibrium
  • Lipids / blood*
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Pennsylvania
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Triglycerides / blood*

Substances

  • Apolipoprotein C-III
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Fats
  • Lipids
  • Triglycerides
  • Cholesterol

Grant support