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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
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
Breslow JL (1985) Human apolipoprotein molecular biology and genetic variation. Annu Rev Biochem 54:699–727
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
Francois J, Lentini F, Hoske P (1977) Genetic study of hyperlipoproteinaemia type IV and V. Clin Genet 12:202–207
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
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
Karathanasis SK, Zannis VI, Breslow JL (1983) Linkage of human apolipoproteins A-1 and C-III genes. Nature 304:371
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
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
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
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
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
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
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
Shoulders CC, Kornblitt AR, Munro S, Baralle FE (1983) Gene structure of human apolipoprotein A-1. Nucleic Acids Res 11:2827–2837
Southern E (1979) Gel electrophoresis of restriction fragments. Methods Enzymol 68:152–175
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
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
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
About this article
Cite this article
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
- Allelic Frequency
- Linkage Disequilibrium
- Restriction Fragment Length Polymorphism
- Restriction Fragment
- Fragment Length Polymorphism