title: Molecular basis of a unique African variant (A-IV 5) of human apolipoprotein A-IV and its significance in lipid metabolism.
abstract: Human apolipoprotein A-IV (apoA-IV) exhibits a genetically determined structural polymorphism amenable to analysis by isoelectric focusing and immunoblotting techniques. We have determined the allele frequency and molecular basis of a unique ApoA-IV*5 allele which is widely distributed among blacks but is absent in other populations. The frequency of the ApoA-IV*5 allele in blacks (N = 308) was estimated to be 3.2%. In comparison to the common ApoA-IV*1 allele, analysis of coding and non-coding sequences of the ApoA-IV*5 allele revealed an in-frame insertion of 12 nucleotides near the carboxyl terminal region of the mature protein. The insertion involves an exact duplication of the second of the four repeats and codes for 4 amino acids glutamic acid (GAA), glutamine (CAG), glutamine (CAG), and glutamine (CAG) and is responsible for the charge shift of the the apoA-IV 5 isoform slightly toward the anode as compared to the wild type apoA-IV 1 isoform on the isoelectric focusing gel. This in-frame insertion occurs in a region which is highly conserved among rat, mouse, and humans. In addition to the 12 nucleotide insertion, the four individuals sequenced for the ApoA-IV*5 allele also revealed a same-sense mutation by replacing G to T at the third position of codon 316. Our preliminary data suggest that this unique black allele marker may be of potentially significance in studies of human lipid metabolism and in microevolution.
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261.
authors: M I
authors: MI
authors: Kamboh
authors: E R
authors: ER
authors: Williams
authors: J C
authors: JC
authors: Law
authors: C E
authors: CE
authors: Aston
authors: C H
authors: CH
authors: Bunker
authors: R E
authors: RE
authors: Ferrell
authors: W S
authors: WS
authors: Pollitzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001054:Apolipoproteins A / Q000235:genetics* / Q000502:physiology*; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013022:South Carolina; D001741:Black or African American
chemical_list: D001054:Apolipoproteins A; C022205:apolipoprotein A-IV; D004247:DNA