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Molecular basis of a unique African Variant (A‐IV 5) of human apolipoprotein A‐IV and its significance in lipid metabolism
Author(s) -
Ilyas Kamboh M.,
Williams Edward R.,
Law John C.,
Aston Christopher E.,
Bunker Clareann H.,
Ferrell Robert E.,
Pollitzer William S.
Publication year - 1992
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.1370090602
Subject(s) - lipid metabolism , apolipoprotein b , genetics , metabolism , biology , biochemistry , cholesterol
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 unqiue black allele marker may be of potentially significance in studies of human lipid metabolism and in microevolution. © 1992 Wiley‐Liss, Inc.