No association of apolipoprotein A-IV codon 347 and 360 variation with atherosclerosis and lipid transport in a sample of mixed hyperlipidemics

Genet Epidemiol. 1995;12(4):371-80. doi: 10.1002/gepi.1370120405.


Genetic variation at the apolipoprotein (apo) A-I/C-III/A-IV gene cluster on chromosome 11 has been associated with differences in occurrence of atherosclerosis and with variability in lipid levels among hypercholesterolemic-hypertriglyceridemic individuals. The functional cause of the association is not known, but polymorphisms of the apo A-IV gene are of interest because apo A-IV is involved in both triglyceride and cholesterol metabolism. Two mutations in the apo A-IV gene, 347T->S and 360Q->H, are known to cause amino acid substitutions in the mature protein. These polymorphisms were typed in a sample of 119 subjects with high cholesterol and high triglycerides in whom carotid artery wall thickness was previously shown to be strongly associated with silent polymorphic variation in the A-I/C-III/A-IV gene cluster. The relative allele frequencies were 0.83 and 0.17 for codon 347T->, and 0.95 and 0.05 for codon 360Q-> H. These polymorphisms did not show a statistically significant relationship with prevalent hypertension, diabetes, or cardiovascular disease or with plasma lipid levels. Most importantly, these amino acids substitutions in apo A-IV were not associated with carotid artery wall thickness. Therefore, the genetic cause of disease variability in a sample of mixed hyperlipidemics is not amino acid substitutions in codons 347 or 360 of the apoliproteins A-IV gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoproteins A / genetics*
  • Arteriosclerosis / genetics*
  • Base Sequence
  • Biological Transport
  • Codon*
  • Female
  • Gene Frequency
  • Genetic Linkage
  • Genetic Variation*
  • Genotype
  • Humans
  • Hyperlipidemias / genetics*
  • Lipid Metabolism*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Risk


  • Apolipoproteins A
  • Codon
  • apolipoprotein A-IV