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

✍ Scribed by Maurita H. Carrejo; A. Richey Sharrett; Wolfgang Patsch; Eric Boerwinkle


Publisher
John Wiley and Sons
Year
1995
Tongue
English
Weight
725 KB
Volume
12
Category
Article
ISSN
0741-0395

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✦ Synopsis


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-8, and 0.95 and 0.05 for codon 360QdH. 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.