Identification of Common Genetic Polymorphisms that Determine Plasma Levels of ApoAI and HDL-C

  • Steve Humphries
  • Vilmundur Gudnason
  • Hiroko Paul-Hayase
  • N. Saha
  • Maryvonne Rosseneu
Part of the NATO ASI Series book series (volume 73)


A large number of epidemiological studies have demonstrated that low serum levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apo AI) are risk factors for the development of coronary artery disease (CAD). Various environmental factors including exogenous gonadal steroids, alcohol intake, stress, infection, the amount of exercise and some drug therapy can significantly affect plasma HDL-C levels. However, there is also good evidence for the involvement of genetic variation in determining these traits, and the heritability of HDL-C and apo AI has been estimated in various studies to be between 0.43 and 0.66 (Hamsten et al 1986). Recently, evidence for a major gene determining individual differences in quantitative levels of apo AI was demonstrated in a population-based sample by applying biometrical techniques (Moll et al 1989).


High Density Lipoprotein Cholesterol Cholesteryl Ester Transfer Protein High Density Lipoprotein Cholesterol Level High Density Lipoprotein Cholesterol Concentration APOAI Level 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson RA, Burns TL, Lee J, Swenson D, Bristow JL (1989) Restriction fragment length polymorphisms associated with abnormal lipid levels in an adolescent population. Atherosclerosis 77: 227–237PubMedCrossRefGoogle Scholar
  2. Bienvenu J, Deshaires P, Bernon H, Armanet P, Peristeris P, Lepape A, Perdrix JP (1988) [Serum amyloid protein A ( SAA) and HDL. Clinical implications and surgical resuscitation.] Ann Biol Clin (Paris) 46: 343–6Google Scholar
  3. Castelli WP, Garrison RJ, Wilson PWF, Abbot RD, Kalousdian S, Kannel WB (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham study. JAMA 256: 2835–8PubMedCrossRefGoogle Scholar
  4. Haffner SM, Applebaum-Bowden D, Wahl PW, Hoover JJ, Warnick GR, Albers JJ, Hazzard WR (1985) Epidemiological correlates of high density lipoprotein subfractions, apolipoprotein AI, All and D and lecithin cholesterol acyltransferase. Effects of smoking, alcohol and adiposity. Arteriosclerosis 5: 169–77Google Scholar
  5. Hamsten A, Iselius L, Dahlen G, Fraire U (1986) Genetic and cultural inheritance of serum lipids low and high density lipoprotein cholesterol and serum apolipoproteins AI, All and B. Atherosclerosis 60: 199–208Google Scholar
  6. Humphries SE (1988) DNA polymorphisms of the apolipoprotein genes -their use in the investigation of the genetic component of hyperlipidaemia and atherosclerosis. Atherosclerosis 72: 89–108PubMedCrossRefGoogle Scholar
  7. Jeenah M, Kessling A, Miller N and Humphries SE (1989) G to A substitution in the promoter region of the Apolipoprotein AI and high density lipoprotein cholesterol concentrations. Mol Biol Med 7: 233–241Google Scholar
  8. Kaprio J, Ferrell RE, Kottke BA, Sing CF (1989) Smoking and reverse cholesterol transport: evidence for gene-environment interaction. Clinic Genet 36: 266–8CrossRefGoogle Scholar
  9. Karathanasis SK (1986) Apolipoprotein multigene family: tandem organisation of apolipoprotein AIV, AI and CIII genes. Proc Natl Acad Sci USA 82: 6374–6378CrossRefGoogle Scholar
  10. Kessling AM, Rajput-Williams J, Bainton D, Scott J, Miller N, Baker I, Humphries SE (1988) DNA polymorphisms of the apolipoprotein All and AI-CIII-AIV genes: a study in men selected for differences in high density lipoprotein cholesterol concentration. Am J Hum Genet 42: 458–67PubMedGoogle Scholar
  11. Kessling AM, Temple A, Taylor A, Hutson J, Hidalgo A, Hidalgo A, Humphries S.E. (1988b) A PvuII polymorphism in the 5’ flanking region of the apo AIV gene: detection of genetic variation determining apo AI and HDL-cholesterol concentration. Human Genetics 78: 237–239.PubMedCrossRefGoogle Scholar
  12. Khaw K-T, Barrett-Conner E (1991) Endogenous sex hormones, high density lipoprotein cholesterol, and other lipoprotein fractions in men. Arteriosclerosis and Thrombosis 11: 489–94PubMedCrossRefGoogle Scholar
  13. Kondo I, Berg K, Drayna D, Lawn R (1989) DNA polymorphism at the locus for human cholesteryl ester transfer protein ( CETP) is associated with high density lipoprotein cholesterol and apolipoprotéin levels. Clinic Genet 35: 49–56Google Scholar
  14. Moll PP, Michels VV, Weidman WH and Kottke BA (1989) Genetic determination of plasma apolipoprotein and AI in a population-based sample. Am J Human Genet 44: 124–139Google Scholar
  15. Morrone G, Cortese R Sorrentino V (1989) Post-transcriptional control of negative acute phase genes by transforming growth factor beta. EMBO-J 8: 3767–71PubMedGoogle Scholar
  16. Ordovas JM, Civeira F, Genest J Jr, Craig S, Robbins AH, Meade T, Pocovi M, Frossard PM, Masharani U, Wilson PWF, Salem DN, Ward RH, Schaefer EJ (1991) Restriction fragment length polymorphisms of the apolipoprotein AI,CIII, AIV gene locus. Relationships with lipids, apolipoproteins and premature coronary artery disease. Atherosclerosis 87: 75–86Google Scholar
  17. Pagani F, Sidoli A, Giudici GA, Barenghi L, Vergani C, Baralle, FE (1990) Human apolipoprotein AI promoter polymorphism: association with hyperlipidaemia. J Lipid Res 31: 1371–1377PubMedGoogle Scholar
  18. Panagiota P, Ogami K, Ramji DP, Nicosia A, Monaci P, Cladaras C, Zannis VI (1991) Promoter elements’and factors involved in hepatic transcription of the human apoA-I gene positive and negative regulators bind to overlapping sites. J Biological Chemistry 266: 5790–5797Google Scholar
  19. Paul-Hayase H, Rosseneu M and Humphries SE (1992) Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations. Hum Genet 88: 439–446PubMedCrossRefGoogle Scholar
  20. Paul-Hayase H, Saha N, Jeenah M, Humphries SE (1992) The G/A substitution in the ApoAI promoter and elevated apoAI levels: Association in men and not in women and test of promoter function (in preparation)Google Scholar
  21. Reichl D, Miller NE (1989) Pathophysiology of reverse cholesterol transport: insights from inherited disorders of lipoprotein metabolism. Arteriosclerosis 9: 785–97PubMedCrossRefGoogle Scholar
  22. Sastry KN, Seedorf U and Karanthansis DK (1988) Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. Mol and Cell Biol 8: 605–614Google Scholar
  23. Shoulders CC, Harry PJ, Lagrost L, White SE, Shah NF, North JD, Gilligan M, Gambert P, Ball MJ (1991) Variation at the apo Ai-CIII-AIV gene complex is associated with elevated plasma levels of apo CIII. Atherosclerosis 87: 239–247PubMedCrossRefGoogle Scholar
  24. Sigurdsson G, Baldursdottir A, Sigvaldason H, Agnarsson U, Thorgeirsson G, Sigfusson N (1992) The predictive value of apolipoproteins in a prospective survey for coronary heart disease in men (submitted)Google Scholar
  25. Sigurdsson G jr, Gudnason V, Sigurdsson G, Humphries S (1992) Interaction between a polymorphism of the apolipoprotein AI promoter ad smoking determines plasma levels of high lipoprotein and apolipoprotein AI. Arteriosclerosis (in press)Google Scholar
  26. Tuomilehto J, Tanskanen A, Salonen JT, Nissinen A, Koskela K (1986) Effect of smoking and stopping smoking on serum high-high density lipoprotein cholesterol levels in a representative population sample. Prey Med 15: 35–45CrossRefGoogle Scholar
  27. Wile DB, Barbir M, Gallagher J, Myant NB, Ritchie CD, Thompson GR, Humphries SE (1989) Apolipoprotein AI gene polymorphisms: frequency in patients with coronary artery disease and healthy controls and association with serum apo AI and HDLcholesterol concentration. Atherosclerosis 78: 9–18PubMedCrossRefGoogle Scholar
  28. Xu C-F, Nanjee MN, Savill J, Talmud P, Angelico F, Del Ben M, Antonini R, Mazzarella B, Miller N, Humphies SE (1990) Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene locus is associated with lipoprotein and apolipoprotein levels in Italian children. Am J Hum Genet 47: 429–439PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Steve Humphries
    • 1
  • Vilmundur Gudnason
    • 1
  • Hiroko Paul-Hayase
    • 1
  • N. Saha
    • 3
  • Maryvonne Rosseneu
    • 2
  1. 1.Centre for the Genetics of Cardiovascular Disorders, Rayne InstituteUniversity College HospitalLondonUK
  2. 2.Clinical ChemistryA-Z St JanBelgium
  3. 3.Department of physiology, Faculty of MedicineNational University of SingaporeKent RidgeSingapore

Personalised recommendations