Young S G, Hubl S T
Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140-0608.
J Lipid Res. 1989 Mar;30(3):443-9.
An apolipoprotein (apo) B-specific monoclonal antibody, MB19, detects a commonly occurring two-allele genetic polymorphism in human apoB (Young, S. G., S. J. Bertics, L. K. Curtiss, D. C. Casal, and J. L. Witztum. 1986. Proc. Natl. Acad. Sci. USA. 83: 1101-1105). Antibody MB19 binds to two different allotypes of apoB, MB19(1) and MB19(2), with high and low affinity, respectively. The epitope for antibody MB19 is located within apoB-100 thrombolytic fragment T4 (apoB-100 amino acid residues 1-1297). In this study, we examined the relationship of the MB19 polymorphism to a C----T nucleotide substitution at apoB cDNA nucleotide 421. This nucleotide substitution results in a Thr----Ile substitution at apoB-100 amino acid 71, and it changes an ApaLI restriction endonuclease site in the apoB gene. The nucleotide substitution was easily detectable by ApaLI digestion of a 141-base pair fragment of the apoB gene obtained by enzymatic amplification of genomic DNA. In 62 subjects, the MB19 phenotype, as determined by radioimmunoassays, correlated perfectly with the ApaLI restriction site polymorphism in the amplified DNA. The apoB allotype MB19(1) is associated with an Ile at residue 71 and the absence of the ApaLI site, whereas the apoB allotype MB19(2) is associated with a Thr at residue 71 and the presence of the ApaLI site. We conclude that the amino acid substitution at residue 71 probably accounts for the MB19 polymorphism in apoB.
