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 clus ter on chromosome 11 has been associated with differences in occurrenc e of atherosclerosis and with variability in lipid levels among hyperc holesterolemic-hypertriglyceridemic individuals. The functional cause of the association is not known, but polymorphisms of the apo A-IV gen e are of interest because apo A-IV is involved in both triglyceride an d cholesterol metabolism. Two mutations in the apo A-IV gene, 347T-->S and 360Q-->H, are known to cause amino acid substitutions in the matu re protein. These polymorphisms were typed in a sample of 119 subjects with high cholesterol and high triglycerides in whom carotid artery w all thickness was previously shown to be strongly associated with sile nt polymorphic variation in the A-I/C-III/A-IV gene cluster. The relat ive 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 stati stically significant relationship with prevalent hypertension, diabete s, or cardiovascular disease or with plasma lipid levels. Most importa ntly, these amino acid substitutions in apo A-IV were not associated w ith carotid artery wall thickness. Therefore, the genetic cause of dis ease variability in a sample of mixed hyperlipidemics is not amino aci d substitutions in codons 347 or 360 of the apolipoprotein A-IV gene. (C) 1995 Wiley-Liss, Inc.