• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. May 15, 1993; 90(10): 4562–4566.
PMCID: PMC46552

An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms.

Abstract

Five DNA polymorphisms were detected in the promoter of the apolipoprotein CIII gene of a type III hyperlipidemic subject with severe hypertriglyceridemia (HTG). The polymorphic sites were C-641-->A, G-630--> A, T-625-->deletion, C-482-->T, and T-455-->C, with the previously reported base at each site designated allele 1 and the variant base designated allele 2. The sites were in strong linkage disequilibrium with each other and with a polymorphic Sst I site in the apolipoprotein CIII 3' untranslated region whose presence (S2 allele) has previously been shown to be associated with HTG. The distribution of haplotypes of the form -625 -482 Sst I among 78 normolipidemic adults and 79 adults with severe HTG was estimated by maximum likelihood analysis. The 211 haplotype was estimated to be 3.8-fold more common in normal subjects than in HTG subjects (estimated proportions, 0.186 and 0.049, respectively). This haplotype was associated with reduced HTG risk (relative risk, 0.28; P = 0.005) when compared with other haplotypes lacking the Sst I site (S1 allele). The 222 haplotype was estimated to be present on 48 of the 54 S2-containing chromosomes observed and was associated with increased risk for HTG (relative risk, 3.14; P < 0.0025). These results support the existence of apolipoprotein CIII promoter/Sst I haplotypes conferring either protection against or susceptibility to severe HTG.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb. 1991 Jan-Feb;11(1):2–14. [PubMed]
  • Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. [PubMed]
  • Bruns GA, Karathanasis SK, Breslow JL. Human apolipoprotein A-I--C-III gene complex is located on chromosome 11. Arteriosclerosis. 1984 Mar-Apr;4(2):97–102. [PubMed]
  • Karathanasis SK. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6374–6378. [PMC free article] [PubMed]
  • Schonfeld G, George PK, Miller J, Reilly P, Witztum J. Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism. 1979 Oct;28(10):1001–1010. [PubMed]
  • Malmendier CL, Lontie JF, Delcroix C, Dubois DY, Magot T, De Roy L. Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients. Effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration. Atherosclerosis. 1989 Jun;77(2-3):139–149. [PubMed]
  • Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL. Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Science. 1990 Aug 17;249(4970):790–793. [PubMed]
  • Wang CS, McConathy WJ, Kloer HU, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest. 1985 Feb;75(2):384–390. [PMC free article] [PubMed]
  • Windler E, Havel RJ. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J Lipid Res. 1985 May;26(5):556–565. [PubMed]
  • Aalto-Setälä K, Fisher EA, Chen X, Chajek-Shaul T, Hayek T, Zechner R, Walsh A, Ramakrishnan R, Ginsberg HN, Breslow JL. Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. J Clin Invest. 1992 Nov;90(5):1889–1900. [PMC free article] [PubMed]
  • Rees A, Shoulders CC, Stocks J, Galton DJ, Baralle FE. DNA polymorphism adjacent to human apoprotein A-1 gene: relation to hypertriglyceridaemia. Lancet. 1983 Feb 26;1(8322):444–446. [PubMed]
  • Ordovas JM, Civeira F, Genest J, Jr, Craig S, Robbins AH, Meade T, Pocovi M, Frossard PM, Masharani U, Wilson PW, et al. Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease. Atherosclerosis. 1991 Mar;87(1):75–86. [PubMed]
  • Taş S. Strong association of a single nucleotide substitution in the 3'-untranslated region of the apolipoprotein-CIII gene with common hypertriglyceridemia in Arabs. Clin Chem. 1989 Feb;35(2):256–259. [PubMed]
  • Shoulders CC, Harry PJ, Lagrost L, White SE, Shah NF, North JD, Gilligan M, Gambert P, Ball MJ. Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII. Atherosclerosis. 1991 Apr;87(2-3):239–247. [PubMed]
  • Reue K, Leff T, Breslow JL. Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors. J Biol Chem. 1988 May 15;263(14):6857–6864. [PubMed]
  • Ogami K, Hadzopoulou-Cladaras M, Cladaras C, Zannis VI. Promoter elements and factors required for hepatic and intestinal transcription of the human ApoCIII gene. J Biol Chem. 1990 Jun 15;265(17):9808–9815. [PubMed]
  • Moreno RF, Booth FR, Hung IH, Tilzer LL. Efficient DNA isolation within a single gel barrier tube. Nucleic Acids Res. 1989 Oct 25;17(20):8393–8393. [PMC free article] [PubMed]
  • Protter AA, Levy-Wilson B, Miller J, Bencen G, White T, Seilhamer JJ. Isolation and sequence analysis of the human apolipoprotein CIII gene and the intergenic region between the apo AI and apo CIII genes. DNA. 1984 Dec;3(6):449–456. [PubMed]
  • Emi M, Wu LL, Robertson MA, Myers RL, Hegele RA, Williams RR, White R, Lalouel JM. Genotyping and sequence analysis of apolipoprotein E isoforms. Genomics. 1988 Nov;3(4):373–379. [PubMed]
  • Huang LS, Kayden H, Sokol RJ, Breslow JL. ApoB gene nonsense and splicing mutations in a compound heterozygote for familial hypobetalipoproteinemia. J Lipid Res. 1991 Aug;32(8):1341–1348. [PubMed]
  • Hixson JE, Vernier DT, Powers PK. Detection of SstI restriction site polymorphism in human APOC3 by the polymerase chain reaction. Nucleic Acids Res. 1991 Jan 11;19(1):196–196. [PMC free article] [PubMed]
  • Hill WG. Estimation of linkage disequilibrium in randomly mating populations. Heredity (Edinb) 1974 Oct;33(2):229–239. [PubMed]
  • Imai E, Stromstedt PE, Quinn PG, Carlstedt-Duke J, Gustafsson JA, Granner DK. Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1990 Sep;10(9):4712–4719. [PMC free article] [PubMed]
  • Schüle R, Muller M, Otsuka-Murakami H, Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature. 1988 Mar 3;332(6159):87–90. [PubMed]
  • O'Brien RM, Bonovich MT, Forest CD, Granner DK. Signal transduction convergence: phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6580–6584. [PMC free article] [PubMed]
  • Stocks J, Paul H, Galton D. Haplotypes identified by DNA restriction-fragment-length polymorphisms in the A-1 C-III A-IV gene region and hypertriglyceridemia. Am J Hum Genet. 1987 Aug;41(2):106–118. [PMC free article] [PubMed]
  • Ahn YI, Valdez R, Reddy AP, Cole SA, Weiss KM, Ferrell RE. DNA polymorphisms of the apolipoprotein AI/CIII/AIV gene cluster influence plasma cholesterol and triglyceride levels in the Mayans of the Yucatán Peninsula, Mexico. Hum Hered. 1991;41(5):281–289. [PubMed]
  • Ferrell RE, Kamboh MI, Majumder PP, Valdez R, Weiss KM. Genetic studies of human apolipoproteins. XIII. Quantitative polymorphism of apolipoprotein C-III in the Mayans of the Yucatán Peninsula. Hum Hered. 1990;40(3):127–135. [PubMed]
  • Smith JD, Brinton EA, Breslow JL. Polymorphism in the human apolipoprotein A-I gene promoter region. Association of the minor allele with decreased production rate in vivo and promoter activity in vitro. J Clin Invest. 1992 Jun;89(6):1796–1800. [PMC free article] [PubMed]
  • Haase A, Stoffel W. The 3'-flanking region shared by the human apolipoprotein AI and CIII gene regulates gene expression in cooperation with 5'-flanking elements. Biol Chem Hoppe Seyler. 1990 Apr;371(4):375–382. [PubMed]
  • Smith GR. Chi hotspots of generalized recombination. Cell. 1983 Oct;34(3):709–710. [PubMed]
  • Kenter AL, Birshtein BK. Chi, a promoter of generalized recombination in lambda phage, is present in immunoglobulin genes. Nature. 1981 Oct 1;293(5831):402–404. [PubMed]
  • Matsuno Y, Yamashiro Y, Yamamoto K, Hattori Y, Yamamoto K, Ohba Y, Miyaji T. A possible example of gene conversion with a common beta-thalassemia mutation and Chi sequence present in the beta-globin gene. Hum Genet. 1992 Jan;88(3):357–358. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...