No association of apolipoprotein A-IV codon 347 and 360 variation with atherosclerosis and lipid transport in a sample of mixed hyperlipidemics.
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.
Human Genetics Center, University of Texas Health Science Center, Houston 77225, USA.
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Carrejo
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Sharrett
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Patsch
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Boerwinkle
D001054:Apolipoproteins A / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics*; D001483:Base Sequence; D001692:Biological Transport; D003062:Codon; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012306:Risk
D001054:Apolipoproteins A; D003062:Codon; C022205:apolipoprotein A-IV