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→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. ©1995 Wiley‐Liss, Inc.
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