Advertisement

Human Genetics

, Volume 82, Issue 4, pp 322–326 | Cite as

Apolipoprotein B amino acid 3611 substitution from arginine to glutamine creates the Ag (h/i) epitope: the polymorphism is not associated with differences in serum cholesterol and apolipoprotein B levels

  • Chunfang Xu
  • Nazeem Nanjee
  • Matti J. Tikkanen
  • Jussi K. Huttunen
  • Pirjo Pietinen
  • Rene Bütler
  • Franco Angelico
  • Maria Del Ben
  • B. Mazzarella
  • R. Antonio
  • Norman G. Miller
  • Steve Humphries
  • Philippa J. Talmud
Original Investigations

Summary

A G-to A-DNA sequence change in exon 26 of the human apolipoprotein B (apo B) gene leads to a glutamine substitution for arginine at codon 3611 of the mature apolipoprotein B100 and causes a loss of an MspI site. In 106 Finnish individuals, a complete correspondence exists between this MspI polymorphic site and the Ag (h/i) immunochemical polymorphism. Linkage disequilibrium was found between this MspI polymorphic site and the apo B XbaI and EcoRI variable sites and the Ag (a1/d) and (c/g) epitope pairs; there is apparent linkage equilibrium with the apo B PvuII variable site. Based on three population studies (samples from London, Finland and Italy), no significant association was found between this RFLP and serum cholesterol and apo B levels. These data suggest that the arginine 3611→glutamine 3611 substitution has no significant effect on apo B function.

Keywords

Cholesterol Internal Medicine Codon Arginine Glutamine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allison AC, Blumberg BS (1961) An isoprecipitation reaction distinguishing human serum-protein types. Lancet I:634–647Google Scholar
  2. Barni N, Talmud PJ, Carlsson P, Azoulay M, Darnfors C, Harding D, Weil D, Grzeschik KH, Bjursell G, Junien C, Williamson R, Humphries SE (1986) The isolation of genomic recombinants for the human apolipoprotein B gene, and the mapping of three common DNA polymorphisms of the gene — a useful marker for human chromosome 2. Hum Genet 73:313–319Google Scholar
  3. Berg K (1979) Inherited lipoprotein variation and atherosclerotic disease. In: Sean AM, Wissler RW, Getz GS (eds) Biochemistry in atherosclerosis. Dekker, New York Basel, pp 419–480Google Scholar
  4. Berg K (1986) DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein levels. Clin Genet 30:515–520Google Scholar
  5. Berg K, Hames C, Dahlen G, Frick MH, Krishan I (1976) Genetic variation in serum low density lipoproteins and lipid levels in man. Proc Natl Acad Sci USA 73:937–940Google Scholar
  6. Berg K, Powell LM, Wallis SC, Pease R, Knott TJ, Scott J (1986) Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: assignment of the Ag locus. Proc Natl Acad Sci USA 83:7367–7370Google Scholar
  7. Blackhart BD, Ludwig EM, Perotti VR, Caiati L, Onasch MA, Wallis SC, Powell L, Pease R, Knott TJ, Mon-LT Chu, Mahley RW, Scott J, McCarthy BJ, Levy-Wilson B (1986) Structure of the human apolipoprotein B gene. J Biol Chem 261:15364–15367Google Scholar
  8. Brown MS, Goldstein JL (1983) Familial hypercholesterolaemia. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited human disease. McGraw-Hill, New York, pp 500–550Google Scholar
  9. Bütler R, Brunner E, Vierucci A, Morganti G (1967) Comparative studies on anti-Ag sera in immunodiffusion and passive haemagglutination methods. Vox Sang 13:327Google Scholar
  10. Bütler R, Brunner E, Morganti G (1974) Contribution to the inheritance of the Ag groups. Vox Sang 26:485–496Google Scholar
  11. Bütler R, Brunner E, Pflugshampt R (1975) Recent progress in the investigation of the Ag-system at beta lipoproteins. In: Peeters H (ed) Protides of the biological fluids, XXIII. Pergamon Press, New York, pp 627–632Google Scholar
  12. Bütler R, Brunner E, Scherz R, Pflugshampt R (1978) Ag system of low density lipoproteins-updating. In: Peeters H (ed) Protides of the biological fluids, XXVI. Pergamon Press, New York, pp 255–262Google Scholar
  13. Chakravarti A, Buetow KH, Antonarakis SE, Waber PG, Boehm CH, Kazazian HK (1984) Non uniform recombination within the human β-globin cluster. Am J Hum Genet 36:1239–1258Google Scholar
  14. Clardaras C, Hadzopoulou-Cladaras M, Nolte RT, Atkinson D, Zannis VI (1986) The complete sequence and structural analysis of human apolipoprotein B-100 relationship between apo B-100 and apo B-48 forms. EMBO J 5:3495–3507Google Scholar
  15. Darnfors C, Nilsson J, Protter AA, Carlsson P, Talmud PJ, Humphries SE, Whalstrom J, Wikland O, Bjursell G (1986) RFLPs for the human apo B gene HincII and PvuII. Nucleic Acids Res 14:7135Google Scholar
  16. Deeb S, Motulsky A, Albers JJ (1985) A partial cDNA clone for human apolipoprotein B. Proc Natl Acad Sci USA 82:4983–4986Google Scholar
  17. Dunning AM, Tikkanen MJ, Ehnholm C, Bütler R, Humphries SE (1988) Relationship between DNA and protein polymorphism of apolipoprotein B. Hum Genet 78:325–329Google Scholar
  18. Duriez P, Vu Dac N, Koffingan M, Puchois P, Demarquilly C, Fievet C, Fievet P, Luyey I, Bard JM, Fourrier JL, Slimane N, Lablanche JM, Bertrand M, Fruchart JC (1987) Detection of human apolipoprotein B polymorphic species with one monoclonal antibody (BIP-45) against low density lipoprotein. Influence of this polymorphism on lipid levels and coronary artery disease. Atherosclerosis 66:153–161Google Scholar
  19. Ehnholm C, Bütler R, Brunner E (1973) The occurrence of Ag determinants in different lipoproteins. Vox Sang 25:281–285Google Scholar
  20. Ehnholm C, Huttunen JK, Pietinen P, Vartiainen E, Leinu U, Mutanen M, Moisio S (1983) Effect of dietary fat on blood pressure in a rural Finnish population. Am J Clin Nutr 38:860Google Scholar
  21. Havekes L, Hammink J, De Wit E (1981) Low density lipoprotein apoprotein B in plasma as measured by radial immunodiffusion and rocket immunoelectrophoresis. Clin Chem 27:1829–1833Google Scholar
  22. Hegele RA, Huang L-S, Herbert PN, Blum CB, Buring JE, Hennekens CH, Breslow JL (1986) Apolipoprotein B-gene DNA polymorphisms associated with myocardial infarction. N Engl J Med 515: 1509–1515Google Scholar
  23. Heiss G, Tyroler HA (1983) Are apolipoproteins useful for evaluating ischaemic heart disease? A brief overview of the literature. In: Proceedings of the workshop on apoliprotein quantification. (NIH publication no 1266) National Institute of Health, Bethesda, Md, pp 7–24Google Scholar
  24. Huang LH, Graaf J, Breslow JL (1988) Apo B gene MspI RFLP in exon 26 changes amino acid 3611 from Arg to Glu. J Lipid Res 239:63–67Google Scholar
  25. Innerarity TL, Weisgraber KH, Arnold KS, Mahley RW, Krauss RM, Vega GL, Grundy SM (1987) Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding. Proc Natl Acad Sci USA 84:6919–6923Google Scholar
  26. Kessling AM, Horsthemke B, Humphries SE (1985) A study of DNA polymorphism around the human apolipoprotein AI gene in hyperlipidaemic and normal individuals. Clin Genet 28:296–306Google Scholar
  27. Knott TJ, Pease RJ, Powell LM, Wallis SC, Rall SC, Innerarity TL, Blackhart B, Taylor WR, Lusis AJ, McCarthy BJ, Mahley RW, Levy-Wilson B, Scott J (1986) Human apolipoprotein B: complete cDNA sequence and identification of structural domains of the protein. Nature 323:734–738Google Scholar
  28. Kunkel LM, Smith KD, Bayer SH, Borgaonkar DS, Wachtel SO, Miller OE, Brey WR, Jones HW, Roury EM (1977) Analysis of human Y-chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249Google Scholar
  29. Law A, Powell LM, Brunt H, Knott TJ, Altman DG, Rajput J, Wallis SC, Pease RJ, Priestley LM, Scott J, Miller GJ, Miller NE (1986) Common DNA polymorphism within coding sequence of apolipoprotein B gene associated with altered lipid levels. Lancet I:1301–1303Google Scholar
  30. Law SW, Grant SM, Higuchi K, Hospattankar A, Lackner K, Lee N, Brewer HB (1986) Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence. Proc Natl Acad Sci USA 83:8142–8146Google Scholar
  31. Lusis AJ, West R, Mehrabian M, Reuben MA, LeBoeuf RC, Kaptein JS, Johnson DF, Schumaker VN, Yuhasz MP, Schotz MC, Elovson J (1985) Cloning and expression of apolipoprotein B, the major protein of low and very low density lipoproteins. Proc Natl Acad Sci USA 82:4597–4601Google Scholar
  32. Ma Y, Schumaker V, Bütler R, Sparkes RS (1987) Two DNA restriction fragment length polymorphisms (RFLPs) associated with Ag(t/z) and Ag (c/g) antigenic sites of human apolipoprotein B. Arteriosclerosis 7:301–305Google Scholar
  33. Protter AA, Hardman DA, Schilling JW, Miller J, Appleby V, Chen GC, Kersher SW, McEnroe G, Kane JP (1986) Isolation of a cDNA clone encoding the amino-terminal region of human apolipoprotein B. Proc Natl Acad Sci USA 83:1467–1471Google Scholar
  34. Sniderman A, Teng B, Terry M (1975) Determination of B protein of low density lipoprotein directly in plasma. J Lipid Res 16:465–469Google Scholar
  35. Soria LF, Ludwig EH, Clarke HRG, Vega GL, Grundy SM, McCarthy BJ (1988) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 86:587–591Google Scholar
  36. Tulmud P, Barni N, Kessling AM, Carlsson P, Darnfors C, Bjursell G, Galton D, Wynn V, Kirk H, Hayden HR, Humphries SE (1987) Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normo-and hyperlipidaemic individuals. Atherosclerosis 67:81–91Google Scholar
  37. Talmud PJ, Lloyd JK, Muller DPR, Collins DR, Scott J, Humphries S (1988) Genetic evidence that the apolipoprotein B gene is not involved in abetalipoproteinemia. J Clin Invest 82:1803–1806Google Scholar
  38. Tikkanen MJ (1987) Immunogenetic polymorphisms of apolipoprotein B in humans: studies with a monoclonal anti-Ag (c) antibody. Am Heart J 113:428–432Google Scholar
  39. Tikkanen MJ, Viikari J, Akerblom HK, Pesonen E (1988) Apolipoprotein B polymorphism and altered apolipoprotein B and low density lipoprotein cholesterol concentrations in Finnish children. Br Med J 296:169Google Scholar
  40. Vega GL, Grundy SM (1986) In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolaemia. J Clin Invest 78:1410–1414Google Scholar
  41. Wang X, Schlapser P, Ma Y, Bütler R, Elovson J, Schumaker VN (1988) Apolipoprotein B. The Ag(a1/d) immunogenetic polymorphism coincides with a T to C substitution at nucleotide 1981, creating an AluI restriction site. Arteriosclerosis 8:429–435Google Scholar
  42. Wile DB, Barbir M, Gallagher J, Myant NB, Ritchie CD, Thompson GR, Humphries SE (1988) Variation at the apolipoprotein AI gene locus is involved in determining plasma apo AI and HDL-cholesterol concentrations in patients with coronary artery disease and healthy controls. Atherosclerosis (in press)Google Scholar
  43. Yang CY, Chen SH, Sparrow JT, Gianturco SH, Bradley WA, Tanimura M, Li W-H, Sparrow DA, De Loof H, Rosseneu M, Pruot L, Brasseur B, Ruysschaert JM, Lee FS, Gu Z-W, Gotto Jr AM, Chan L (1986) Sequence, structure, receptor-binding domains and internal repeat of human apolipoprotein B-100. Nature 323:738–742Google Scholar
  44. Young SG, Bertics SJ, Curtiss LK, Casal DC, Witztum JL (1986) Monoclonal antibody MB19 detects genetic polymorphism in human apolipoprotein B. Proc Natl Acad Sci USA 83:1101–1105Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Chunfang Xu
    • 1
  • Nazeem Nanjee
    • 2
  • Matti J. Tikkanen
    • 3
  • Jussi K. Huttunen
    • 4
  • Pirjo Pietinen
    • 4
  • Rene Bütler
    • 5
  • Franco Angelico
    • 6
  • Maria Del Ben
    • 6
  • B. Mazzarella
    • 6
  • R. Antonio
    • 6
  • Norman G. Miller
    • 2
  • Steve Humphries
    • 1
  • Philippa J. Talmud
    • 1
  1. 1.Charing Cross Sunley Research CentreLondonUK
  2. 2.The Bowman Gray School of MedicineWake Forest UniversityWinston-SalemUSA
  3. 3.Third Department of MedicineUniversity Centre HospitalHelsinkiFinland
  4. 4.National Public Health InstituteHelsinkiFinland
  5. 5.Central LaboratoryBlood Transfusion Service of the Swiss Red CrossBerne 22Switzerland
  6. 6.Instituto di Teratia Medica Sistematicadell Università la Sapienza di RomaRomeItaly

Personalised recommendations