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Familial combined hyperlipidaemia linked to the apolipoprotein AI–CIII–AIV gene cluster on chromosome 11q23q–q24

Nature volume 349, pages 161–164 (1991)Cite this article

Abstract

FAMILIAL combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5–2.0% (refs 1,2). It is estimated to cause 10% of premature coronary heart disease1,3. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI–CIII–AIV gene cluster4. Here we confirm this association and show that it results from linkage disequilibrium between FCHL and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FCHL families, ascertained through a proband carrying the 6.6 kbXmnI allele, demonstrated linkage to the AI–CIII–AIV cluster on 1lq23–q24, ẑ= 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.

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References

  1. Grundy, S. M., Chait, A. & Brunzell, J. D. Arteriosclerosis 7, 203–207 (1987).

    Google Scholar 

  2. Goldstein, J. L., Schrott, H. G., Hazzard, W. R., Bierman, E. L. & Motulsky, A. G. J. clin. Invest 52, 1544–1568 (1973).

    Article  CAS  Google Scholar 

  3. Brunzell, J. D., Schrott, H. G., Motulsky, A. G. & Bierman, E. L. Metabolism 25, 313–320 (1976).

    Article  CAS  Google Scholar 

  4. Hayden, M. R. et al. J. Am. J. hum. Genet. 40, 421–430 (1987).

    CAS  Google Scholar 

  5. Nikkilä, E. A. & Aro, A. Lancet i, 954–958 (1973).

    Article  Google Scholar 

  6. Rose, H. G., Kranz, P., Weinstock, M., Juliano, J. & Haft, J. I. Am. J. Med. 54, 148–160 (1973).

    Article  CAS  Google Scholar 

  7. Teng, B. Proc. natn. Acad. Sci. USA 80, 6662–6666 (1983).

    Article  ADS  CAS  Google Scholar 

  8. Kessling, A. M., Horsthemke, B. & Humphries, S. E. Clin. Genet. 28, 296–306 (1985).

    Article  CAS  Google Scholar 

  9. Lipid Research Clinics Population Studies Data Book, Vol. 1 The Prevalence Study (NIH Publication No. 80–1527, July 1980).

  10. Law, A. et al. Lancet i, 1301–1303 (1986).

    Article  Google Scholar 

  11. Ott, J. Genet Epidemiol. 2, 79–84 (1985).

    Article  CAS  Google Scholar 

  12. Babirak, S. P., Iverius, P., Fujimoto, W. Y. & Brunzell, J. D. Arteriosclerosis 9, 326–334 (1989).

    Article  CAS  Google Scholar 

  13. Griffin, B. J. et al. Atherosclerosis 83, 59–67 (1990).

    Article  CAS  Google Scholar 

  14. Lander, E. S. Mapping complex genetic traits in humans in Genome Analysis, A Practical Approach (ed. Davies, K. E.) 171–189 (IRL, Oxford, 1988).

    Google Scholar 

  15. Wilson, T. M. E. et al. Nucleic Acids Res. (in the press).

  16. Lathrop, G. M. et al. Proc. natn. Acad. Sci. USA 81, 3443–3446 (1984).

    Article  ADS  CAS  Google Scholar 

  17. Conneally, P. M. et al. Cytogenet. Cell Genet. 40, 356–359 (1985).

    Article  CAS  Google Scholar 

  18. Norum, R. A. et al. New Eng. J. Med. 306, 1513–1519 (1982).

    Article  CAS  Google Scholar 

  19. Breslow, J. L. J. clin. Invest. 84, 373–380 (1989).

    Article  CAS  Google Scholar 

  20. Goldberg, I. J., Scheradi, C. A., Yakoub, L. K., Saxena, U. & Biggaier, C. L. J. biol. Chem. 8, 4266–4272 (1990).

    Google Scholar 

  21. Windier, E. & Havel, R. J. J. Lipid Res. 26, 556–565 (1985).

    Google Scholar 

  22. Ginsberg, H. N. et al. J. clin. Invest. 78, 1287–1295 (1986).

    Article  CAS  Google Scholar 

  23. Chivot, L. et al. Atherosclerosis 82, 205–211 (1990).

    Article  CAS  Google Scholar 

  24. Friedewald, W. T., Levy, R, I. & Fredrickson, D. S. Clin. Chem. 18, 499–502 (1972).

    CAS  PubMed  Google Scholar 

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Author notes

  1. James Scott: To whom correspondence should be addressed.

Authors and Affiliations

  1. Division of Molecular Medicine, MRC Clinical Research Centre, Northwich Park Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, UK

    Andrew P. Wojciechowski, Martin Farrall, Paul Cullen, Teresa M. E. Wilson, Jayne D. Bayliss, Bernadette Farren, Rajesh Thakker & James Scott

  2. Institute of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, G4 OSF, UK

    Bruce A. Griffn, Muriel J. Caslake, Christopher J. Packard & James Shepherd

Authors
  1. Andrew P. Wojciechowski
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  2. Martin Farrall
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  4. Teresa M. E. Wilson
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  6. Bernadette Farren
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  7. Bruce A. Griffn
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  8. Muriel J. Caslake
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  11. Rajesh Thakker
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Wojciechowski, A., Farrall, M., Cullen, P. et al. Familial combined hyperlipidaemia linked to the apolipoprotein AI–CIII–AIV gene cluster on chromosome 11q23q–q24. Nature 349, 161–164 (1991). https://doi.org/10.1038/349161a0

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