J. Biol. Chem., Vol. 266, Issue 21, 13513-13518, 07, 1991

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)

P Lohse, MR Kindt, DJ Rader and HB Brewer Jr
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

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.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. R. Tubb, R. A. G. D. Silva, K. J. Pearson, P. Tso, M. Liu, and W. S. Davidson Modulation of Apolipoprotein A-IV Lipid Binding by an Interaction between the N and C Termini J. Biol. Chem., September 28, 2007; 282(39): 28385 - 28394. [Abstract] [Full Text] [PDF]

				W.-m. R. Wong, J. W. Stephens, J. Acharya, S. J. Hurel, S. E. Humphries, and P. J. Talmud The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease J. Lipid Res., August 1, 2004; 45(8): 1565 - 1571. [Abstract] [Full Text] [PDF]

				S. Jansen, J. Lopez-Miranda, J. Salas, J. M. Ordovas, P. Castro, C. Marin, M. A. Ostos, F. Lopez-Segura, J. A. Jimenez-Pereperez, A. Blanco, et al. Effect of 347-Serine Mutation in Apoprotein A-IV on Plasma LDL Cholesterol Response to Dietary Fat Arterioscler. Thromb. Vasc. Biol., August 1, 1997; 17(8): 1532 - 1538. [Abstract] [Full Text]