NO ASSOCIATION OF APOLIPOPROTEIN A-IV CODON-347 AND CODON-360 VARIATION WITH ATHEROSCLEROSIS AND LIPID TRANSPORT IN A SAMPLE OF MIXED HYPERLIPIDEMICS

Genetic variation at the apolipoprotein (ape) 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-->S, 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 acid 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 apolipoprotein A-IV gene. (C) 1995 Wiley-Liss, Inc.