Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene.
Genetic polymorphism of human plasma apolipoprotein A-IV has been detected by isoelectric focusing techniques followed by immunoblotting. The molecular basis for this apoA-IV polymorphism has been elucidated. Analysis of the protein coding sequences of the apoA-IV alleles 1 and 2 revealed a single G to T substitution in the apoA-IV-2 allele. The point mutation, occurring in a region highly conserved among the mouse, rat, and human A-IV apolipoproteins, converts the glutamine at position 360 of the mature protein to a histidine. This amino acid substitution adds one positive charge unit to the apoA-IV-1 isoprotein (pI 4.97) thus creating the more basic apoA-IV-2 isoprotein (pI 5.02). Computer analysis of the apoA-IV-2 allele revealed that the single G to T substitution results in the loss of a BbvI and a Fnu4HI restriction enzyme site and in the formation of a new restriction site for the enzyme SfaNI. Protein primary and secondary structure predictions were largely unaffected by this amino acid exchange. These results on the structure of the apoA-IV-1 and apoA-IV-2 alleles suggest that the three other rare isoproteins (apoA-IV-0, apoA-IV-3, and apoA-IV-4) are also due to nucleotide and subsequent amino acid substitutions in the apoA-IV sequence.
Lohse
P
P
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kindt
M R
MR
Rader
D J
DJ
Brewer
H B
HB
D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D005796:Genes; D006801:Humans; D007525:Isoelectric Focusing; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010641:Phenotype; D011110:Polymorphism, Genetic; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D001054:Apolipoproteins A; D015345:Oligonucleotide Probes; C022205:apolipoprotein A-IV