Skip to main content
SpringerLink
Log in

Genetic Risk Factors for Coronary Heart Disease in the Japanese Population

  • Conference paper
Genetic Approaches to Coronary Heart Disease and Hypertension

Summary

Our recent data on genes associated with premature coronary heart disease (CHD) or possibly involved in CHD in the Japanese population are described. Frequency distributions, mean values and median values of plasma lipoprotein (a) (Lp(a)) concentrations in a Japanese population are similar to those in most Caucasians. Preliminary data suggest that apolipoprotein (a) is also highly polymorphic in the Japanese population. Furthermore, in inactive plasminogen, phenotype M5, is polymorphic in the Japanese. Data obtained with polymerase chain reaction (PCR) and allele-specific oligonucleotide probes indicate that plasminogen M5 has a codon 601 missense mutation (GCT → ACT, Ala → Thr) and is identical with plasminogen Tochigi. As to apolipoprotein (apo) E polymorphisms, data obtained with PCR and allele-specific oligonucleotide probes suggest that many of apo E-2 have the codon 158 missense mutation (CGC → TGC, Arg → Cys) and that most, if not all, of apo E-4 have the codon 112 missense mutation (TGC → CGC, Cys → Arg) in the Japanese. The frequencies of alleles for apo E-2 and E-4, however, is lower in Japanese than in most Caucasians. As regarding familial hypercholesterolemia (FH), whose heterozygote frequency is estimated to be 1 in 500 persons in the Japanese, data obtained with family studies of the low density lipoprotein (LDL) receptor gene suggest that most, if not all, of relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defect of the LDL receptor gene, and that the origin of the mutant LDL receptor gene generally differs among different pedigrees in the Japanese population. On the other hand, data obtained by population and family studies suggest that hereditary moderate hypercholesterolemia due to abnormal gene(s) distinct from the abnormal LDL receptor gene may be more common than classic FH. As to the apolipoprotein A-I (apoA-I) gene, a mutant apoA-I gene with a codon 84 nonsense mutation which caused apoA-I deficiency, a marked reduction of HDL cholesterol and premature CHD is described. This finding suggests that a mutant apoA-I gene can act as a major gene for decreased levels of apoA-I and HDL cholesterol. Finally, application of genetic data for the prevention of premature CHD are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Assman G, Schmitz G, Funke H, von Eckardstein A (1990) Apolipoprotein A-I and HDL deficiency. Curr Opin Lipidol 1: 110–115

    Article  Google Scholar 

  2. Boerwinkle E, Sing CF (1987) The use of measured genotype information in the analysis of quantitative phenotypes in man. Ann Hum Genet 51: 211–226

    Article  PubMed  CAS  Google Scholar 

  3. Boerwinkle E, Visvikis S, Welsh D, Steinmetz J, Hanash SM, Sing CF (1987) The use of measured genotype information in the analysis of quantitative phenotype in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals. Am J Med Genet 27: 567–582

    Article  PubMed  CAS  Google Scholar 

  4. Breslow JL (1989) Familial disorders of high density lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 1251–1266

    Google Scholar 

  5. Cumming AM, Robertson FW (1984) Polymorphism at the apoprotein-E locus in relation ro risk of coronary disease. Clin Genet 25: 310–313

    Article  PubMed  CAS  Google Scholar 

  6. Ehnholm C, Lukka M, Kuusi T, Nikkila E, Utermann G (1986) Apolipoprotein E polymorphism in the Finish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res 27: 227–235

    PubMed  CAS  Google Scholar 

  7. Eto M, Watanabe K, Ishii K (1986) A racial difference in apolipoprotein E allele frequencies between the Japanese and Caucasian populations. Clin Genet 30: 422–427

    Article  PubMed  CAS  Google Scholar 

  8. Gaubatz JW, Ghanem KI, Guevera J, Nava ML, Patsch W, Morrisett JD (1990) Polymorphic forms of human apolipoprotein(a): inheritance and relationship of their molecular weights to plasma levels of lipoprotein (a). J Lipid Res 31: 603–613

    PubMed  CAS  Google Scholar 

  9. Goldstein JL, Brown MS (1989) Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edition. McGraw-Hill, New York, pp 1215–1250

    Google Scholar 

  10. Gustafson A, McConathy WJ, Alaupovic P, Persson B (1979) Identification of lipoprotein families in a variant of human plasma apolipoprotein A deficiency. Scand J Clin Invest 39: 377–387

    Article  PubMed  CAS  Google Scholar 

  11. Hiasa H, Maeda T, Mori H (1986) Deficiency of apolipoproteins A-I and C-III and severe coronary heart disease. Clin Cardiol 9: 349–352

    Article  PubMed  CAS  Google Scholar 

  12. Karathanasis SK, Ferris E, Haddad IA (1987) DNA inversion within the apolipoprotein AI/CIII/AIV-encoding gene cluster of certain patients with premature atherosclerosis. Proc Natl Acad Sci USA 84: 7198–7202

    Article  PubMed  CAS  Google Scholar 

  13. Lehtimaki T, Moilanen T, Viikari J, Akerblom HK, Ehnholm C, Ronnemaa T, Marniemi J, Dahlen G, Nikkari T (1990) Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res 31: 487–495

    PubMed  CAS  Google Scholar 

  14. Mabuchi H, Tatami R, Haba T, Ueda K, Ueda R, Kametani T, Itoh S, Koizumi J, Ohta M, Miyamoto S, Takeda R, Takeshita H (1978) Homozygous familial hypercholeterolemia in Japan. Am J Med 65: 290–297

    Article  PubMed  CAS  Google Scholar 

  15. Mabuchi H, Tatami R, Ueda K, Ueda R, Haba T, Kametani T, Watanabe A, Wakasugi T, Ito S, Koizumi J, Ohta M, Miyamoto S, Takeda R (1979) Serum lipid and lipoprotein levels in Japanese patients with familial hypercholesterolemia. Atherosclerosis 32: 435–444

    Article  PubMed  CAS  Google Scholar 

  16. Mahley RW, Rall SC (1989) Type III hyperlipoproteinemia (Dysbetalipoproteinemia). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, Yew York, pp 1195–1213

    Google Scholar 

  17. Menzel HJ, Kladetzky RG, Assmann G (1983) Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 3: 310–315

    Article  PubMed  CAS  Google Scholar 

  18. Miyata T, Iwanaga S, Sakata Y, Aoki N (1982) Plasminogen Tochigi: Inactive plasmin resulting from replacement of alanine-600 by threonine in the active site. Proc Natl Acad Sci USA 79: 6132–6136

    Article  PubMed  CAS  Google Scholar 

  19. Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block WD, Nofze DK, Dolphin PJ, Edelglass J, Bogorad DD, Alaupovic P (1982) Familial deficiency of apolipoprotein A-I and C-III and precocious coronary-artery disease. N Engl J Med 306: 1513–1519

    Article  PubMed  CAS  Google Scholar 

  20. Ordovas JM, Litwack-Klein L, Wilson PWF, Schaefer MM, Schaefer EJ (1987) Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoEl and apoE5 isoforms. J Lipid Res 28: 371–380

    PubMed  CAS  Google Scholar 

  21. Ordovas JM, Cassidy DK, Civcira F, Bisgaier CL, Schaefer EJ (1989) Familial apolipoprotein A-I, C-III, and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11. J Biol Chem 264: 16339–16342

    PubMed  CAS  Google Scholar 

  22. Petersen TE, Martzen MR, Ichinose A, Davie EW (1990) Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem 265: 6104–6111

    PubMed  CAS  Google Scholar 

  23. Scanu AM, Fless GM (1990) Lipoprotein (a). J Clin Invest 85: 11709–1715

    Article  Google Scholar 

  24. Schaefer EJ, Ordovas JM, Law SW, Ghiselli G, Kashyap ML, Srivastava LS, Heaton WH, Albers JJ, Connor WE, Lindgren FT, Lemeshev Y, Segrest JP, Brewer HB (1985) Familial apolipoprotein A-I and C-III deficiency, variant II. J Lipid Res 26: 1089–1101

    PubMed  CAS  Google Scholar 

  25. Smit M, de Knijff P, Rosseneu M, Bury J, Klasen E, Frants R, Havekes L (1988) Apolipoprotein E polymorphism in the Netherlands and its effect on plasma lipid and apolipoprotein levels. Human Genet 80: 287–292

    Article  CAS  Google Scholar 

  26. Smit M, de Knijff P, van der Kooij-Meijs E, Groenendijk C, van den Maagdenberg AMJM, Leuven JAG, Stalenhoef AFH, Stuyt PMJ, Frants RR, Havekes LM (1990) Genetic heterogeneity in familial dysbetalipoproteinemia. The E2(Lys146üGln) variant results in a dominant mode of inheritance. J Lipid Res 31: 45–53

    PubMed  CAS  Google Scholar 

  27. Soria LF, Ludwig EH, Clarke HRG, Vega GL, Grundy SM, McCarthy BJ (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 86: 587–591

    Article  PubMed  CAS  Google Scholar 

  28. Utermann G, Steinmets A, Weber W (1982) Genetic control of human apolipoprotein E polymorphism: Comparison of one-and two-dimensional techniques of isoprotein analysis. Human Genet 60: 344–351

    Article  CAS  Google Scholar 

  29. Utermann G (1989) The mysteries of lipoprotein (a). Science 246: 904–910

    Article  PubMed  CAS  Google Scholar 

  30. Yamaguchi M, Doi S, Yoshimura M (1989) Plasminogen phenotypes in a Japanese population. Human Hered 39: 356–360

    Article  CAS  Google Scholar 

  31. Yamakawa K, Okafuji T, Iwamura Y, Yuzawa K, Satoh J, Hattori N, Yamanouchi Y, Yanagi H, Kawai K, Tsuchiya S, Russell DW, Hamaguchi H (1988) TaqI polymorphism in the LDL receptor gene and a TaqI 1.5-kb band associated with familial hypercholesterolemia. Human Genet 80: 1–5

    Article  CAS  Google Scholar 

  32. Yamakawa K, Takada K, Yanagi H, Tsuchiya S, Kawai K, Nakagawa S, Hamaguchi H (1989) Three novel partial deletions of the low-density lipoprotein gene in familial hypercholesterolemia. 82: 317–321

    CAS  Google Scholar 

  33. Yamakawa K, Yanagi H, Saku K, Sasaki J, Okafuji T, Shimakura Y, Kawai K, Tsuchiya S, Takada K, Naito S, Arakawa K, Hamaguchi H. Family studies of the LDL receptor gene of relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas. Human Genet in press

    Google Scholar 

  34. Janagi H, Shimakura Y, Yamanouchi Y, Watanabe Y, Tsuchiya S, Hamaguchi H (1990) Association of hypercholesterolemia and apolipoprotein E4 in school children. Clin Genet 38: 264–269

    Google Scholar 

  35. Yuzawa K, Yamakawa K, Tohno E, Seki M, Akisada M, Yanagi H, Okafuji T, Yamanouchi Y, Hattori N, Kawai K, Shimakura Y, Tsuchiya S, Ijima H, Fukao K, Iwasaki Y, Hamaguchi H (1989) An ultrasonographic method for detection of Achilles tendon xanthomas in familial hypercholesterolemia. Atherosclerosis 75: 211–218

    Article  PubMed  CAS  Google Scholar 

  36. Wardell MR, Suckling PA, Janus ED (1982) Genetic variation in human apolipoprotein E. J Lipid Res 23: 1174–1182

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. H. Hamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Yanagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Matsunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Yamanouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y. Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y. Shimakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N. Imoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Arinami
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K. Yamakawa-Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Medical Genetics, UllevalHospital, University of Oslo, Oslo, Norway

    Kare Berg M. D., Ph. D.

  2. World Health Organization, Avenue Appia, 1211, Geneva 27, Switzerland

    Victor Bulyzhenkov

  3. Fondation IPSEN pour la Recherche, Thérapeutique, 30, rue Cambronne, F-75737, Paris Cedex, France

    Yves Christen

  4. INSERM Unit 36, Collège de France, 3 rue d’Ulm, F-75005, Paris, France

    Pierre Corvol M. D.

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hamaguchi, H. et al. (1991). Genetic Risk Factors for Coronary Heart Disease in the Japanese Population. In: Berg, K., Bulyzhenkov, V., Christen, Y., Corvol, P. (eds) Genetic Approaches to Coronary Heart Disease and Hypertension. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76891-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76891-0_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76893-4

  • Online ISBN: 978-3-642-76891-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation