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haplotypes identified by DNA polymorphisms at the apolipoprotein A-1 and C-III loci and hypertriglyceridaemia

A study in a Japanese population

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Summary

A Japanese group comprising 40 hypertriglyceridaemic and 35 normolipidaemic subjects were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) at the A-1 and C-III gene loci. An Sst-1 polymorphism is located at the 3′ end of the C-III gene and a Msp-1 polymorphism in the third intron of the A-1 gene. The polymorphic restriction sites are 3.8kb apart. The polymorphism with Sst-1 was present at allelic frequencies of 0.67 (S1 allele) and 0.33 (S2 allele), and the polymorphism with Msp-1 was present at allelic frequencies of 0.55 (M1 allele) and 0.45 (M2 allele). The alleles S1, S2, M1, and M2 are in linkage disequilibrium and three haplotypes were identified S1-M1, S1-M2, and S2-M2. Unlike the previously reported association of the S2 allele with hypertriglyceridaemia found in Caucasians there was no difference in the frequency of S2 allele between normolipidaemic and hyperlipidaemic Japanese. However one of the haplotypes S1-M2 was significantly increased in the hypertriglyceridaemic subjects (32% versus 11% P>0.025). Thus in Japanese there is an association with genotypes at this locus and hypertriglyceridaemia but with a different haplotype than in Caucasians.

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References

  1. Bell GI, Karam JH, Rutter WJA (1981) Polymorphic region adjacent to the 5′ end of the human insulin gene. Proc Natl Acad Sci USA 78:5759–5763

  2. Breslow JL (1985) Human apolipoprotein molecular biology and genetic variation. Annu Rev Biochem 54:699–727

  3. Chi-Sun Wang, Mconathy WJ, Kloer H, Alaupovic P (1985) Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest 75:384–390

  4. Francois J, Lentini F, Hoske P (1977) Genetic study of hyperlipoproteinaemia type IV and V. Clin Genet 12:202–207

  5. Holdsworth G, Stocks J, Dodson P, Galton DJ (1982) An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III. J Clin Invest 69:932–939

  6. Humphries SE, Kessling AM, Horsthemke B, Donald J, Seed M, Jowett N, Holm M, Galton DJ, Wynn V, Williamson R (1985) A common DNA polymorphism of the low density lipoprotein (LDL) receptor gene and its use in diagnosis. Lancet I:1003–1006

  7. Karathanasis SK, Zannis VI, Breslow JL (1983) Linkage of human apolipoproteins A-1 and C-III genes. Nature 304:371

  8. Menzel HJ, Assman G, Rall RC, Rall SC, Weisgraber KH, Mahley RW (1984) Human apolipoprotein A-1 gene polymorphism. J Biol Chem 259:3070–3076

  9. Myklebost O, Rogne S, Olaisen B, Gedde-Dahl T, Prydz H (1984) The locus for apolipoprotein C-II is closely linked to the apolipoprotein E locus on chromosome 19 in man. Hum Genet 67:309–312

  10. Protter AA, Levy-Wilson B, Miller J, Bencen G, White T, Seilhamer JJ (1984) Isolation and sequence analysis of the human apolipoprotein C-III gene and the intergenic region between the apo A-1 and apo C-III genes. DNA 3:449–456

  11. Rees A, Shoulders CC, Stocks J, Galton DJ, Baralle FE (1983) DNA polymorphism adjacent to human apoprotein A-1 gene—relation to hypertriclyceridaemia. Lancet I:444–446

  12. Rees A, Sharpe C, Stocks J, Vella MA, Shoulders CC, Katz J, Jowitt N, Baralle FE, Galton DJ (1985) DNA polymorphism in the apo A1-C-III gene cluster. Association with hypertriglyceridaemia. J Clin Invest 76:1090–1095

  13. Scott J, Knott TJ, Priestley LM, Robertson ME, Mann DV, Kostner G, Miller GJ, Miller NE (1985) High density lipoprotein composition is altered by a common DNA polymorphism adjacent to apoprotein A-II gene in man. Lancet I:771–773

  14. Seilhamer JT, Protter AA, Frossard P, Levy-Wilson B (1984) Isolation and DNA sequence of full-length cDNA and of the entire gene for human apolipoprotein A-1. Discovery of a new genetic polymorphism in the apo A-1 gene. DNA 3:309–317

  15. Shoulders CC, Kornblitt AR, Munro S, Baralle FE (1983) Gene structure of human apolipoprotein A-1. Nucleic Acids Res 11:2827–2837

  16. Southern E (1979) Gel electrophoresis of restriction fragments. Methods Enzymol 68:152–175

  17. Stocks J, Holdsworth G, Galton DJ (1979) Hypertriglyceridaemia associated with an abnormal triglyceride-rich lipoprotein carrying excess apolipoprotein C-III-2. Lancet II:667–671

  18. Windler E, Chao Y, Havel RJ (1980) Determinants of hepatic uptake of triglyceride-rich lipoproteins and their remanants in the rat. J Biol Chem 255:5475–5480

  19. Vella M, Kessling A, Jowett N, Rees A, Stocks J, Wallis S, Galton DJ (1985) DNA polymorphisms flanking the apo A-1 and insulin genes and type III hyperlipidaemia. Hum Genet 69:275–276

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Correspondence to J. Stocks.

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Rees, A., Stocks, J., Paul, H. et al. haplotypes identified by DNA polymorphisms at the apolipoprotein A-1 and C-III loci and hypertriglyceridaemia. Hum Genet 72, 168–171 (1986). https://doi.org/10.1007/BF00283939

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Keywords

  • Allelic Frequency
  • Linkage Disequilibrium
  • Restriction Fragment Length Polymorphism
  • Restriction Fragment
  • Fragment Length Polymorphism