Three genetic variants of human plasma apolipoprotein A-IV. apoA-IV-1(Thr347----Ser), apoA-IV-0(Lys167----Glu,Gln360----His), and apoA-IV-3(Glu165----Lys).
Human apolipoprotein (apo) A-IV is a genetically polymorphic glyco-protein of 376 residues. We have recently reported the molecular basis for the two most common isoproteins, apoA-IV-1 and apoA-IV-2(Gln360----His), and for two rare variants, apoA-IV-0 (4-amino acid insertion) and apoA-IV-3(Glu230----Lys). In this report, we present the genetic basis for three additional isoproteins of apoA-IV. Sequence analysis of the apoA-IV-1 allele revealed a common nucleotide substitution which converts threonine (ACT), residue 347 of the mature protein, into serine (TCT). In one out of the five subjects with the apoA-IV-1/0 phenotype we identified two point mutations: 1) replacing the positively charged lysine (AAG), amino acid 167, with a negatively charged glutamic acid (GAG), and 2) converting the neutral residue 360, glutamine (CAG), to a positively charged histidine (CAT). We have also characterized four additional heterozygotes for the apoA-IV-3 allele. One individual was found to have the previously described substitution of lysine for glutamic acid at amino acid 230. The three other subjects had the identical mutation but at a different position in the polypeptide chain, residue 165. These results indicate that one predominant allele codes for the isoproteins apoA-IV-2 and apoA-IV-0 and that at least two major allelic variants for the isoproteins apoA-IV-1 and apoA-IV-3 are present in the population analyzed.
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
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D001054:Apolipoproteins A; C022205:apolipoprotein A-IV