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DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels

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Summary

Lipoprotein lipase (LPL) plays a central role in the metabolism of lipoproteins by hydrolyzing the core triglycerides of circulating very low density lipoproteins and chylomicrons. The enzyme is encoded by a gene about 30kb in size located on the short arm of human chromosome 8. We have determined the locations of the four common DNA polymorphisms along the gene, including a polymorphism that occurred only among an American black population examined. These restriction site polymorphisms were used for haplotype analysis of Mediterranean and US black families. Estimation of the extent of nonrandom association between these polymorphisms indicated considerable linkage disequilibrium between these sites. No correlation was observed between the level of linkage disequilibrium and the physical distance of the polymorphic sites. The polymorphism information content of the haplotypes ranged from 0.65 to 0.74, thereby constituting a relatively useful genetic marker on chromosome 8. We tested for possible associations between the polymorphisms and circulating lipoprotein phenotypes in a population of 139 Caucasians undergoing coronary arteriography and 50 of their spouses. Some possibly significant associations between LPL gene polymorphisms and levels of high density lipoprotein cholesterol (P = 0.015) and total plasma cholesterol (P = 0.025) were observed. In contrast to a previous report, we found no significant associations with the levels of plasma triglycerides.

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References

  • Antonarakis SE, Oettgen P, Chakravarti A, Halloran SL, Hudson RR, Feisee L, Karathanasis SK (1988) DNA polymorphism haplotypes of the human apolipoprotein APOA1-APOC3-APOA4 gene cluster. Hum Genet 80:265–273

    Google Scholar 

  • Applebaum-Bowden D, Haffner SM, Wahl PW, Hoover JJ, Warnick GR, Albers JJ, Hazzard WR (1985) Post-heparin plasma triglyceride lipases: relationships with very low density lipoprotein triglyceride and high density lipoprotein2 cholesterol. Arteriosclerosis 5:273–282

    Google Scholar 

  • Babirak SP, Iverius PH, Fujimoto WY, Brunzell J (1989) Detection and charaterization of the heterozygote state for lipoprotein lipase deficiency. Arteriosclerosis 9:326–334

    Google Scholar 

  • Borresen AL, Moller P, Berg K (1988) Linkage disequilibrium analyses and restriction mapping of four RFLP's at the proα2(1) collagen locus: lack of correlation between linkage disequilibrium and physical distances. Hum Genet 78:216–221

    Google Scholar 

  • Breslow JL (1989) Genetic basis of lipoprotein disorders. J Clin Invest 84:373–380

    Google Scholar 

  • Chakravarti A, Buetow KH, Antonarakis SE, Weber PG, Boehm CD, Kazazian HH Jr (1984) Nonuniform recombination with the human β-globin gene cluster. Am J Hum Genet 36:1239–1258

    Google Scholar 

  • Chakravarti A, Elbein SC, Permutt MA (1986) Evidence for increased recombination near the human insulin gene: implication for disease association studies. Proc Natl Acad Sci USA 83:1045–1049

    Google Scholar 

  • Chamberlain JC, Thorn JA, Oka K, Galton DJ, Stocks J (1989) DNA polymorphisms at the lipoprotein lipase gene: associations in normal and hypertriglyceridaemic subjects. Atherosclerosis 79:85–91

    Google Scholar 

  • Ewens WJ (1983) The role of models in the analysis of the molecular genetic data with particular reference to restriction fragment data. In: Weir BS (ed) Statistical analysis of DNA sequence data. Dekker, New York, pp 45–73

    Google Scholar 

  • Fisher KL, Fitzgerald GA, Lawn R (1987) Two polymorphisms in the human lipoprotein lipase (LPL) gene. Nucleic Acids Res 15:7567

    Google Scholar 

  • Funke H, Reckwerth A, Stapenhorst D, Schulze Beiering M, Jansen M, Assman G (1988) BstNI (EcoRII) RFLP in the lipoprotein lipase gene (LPL). Nucleic Acids Res 16:2741

    Google Scholar 

  • Garfinkel AS, Schotz MC (1987) Lipoprotein lipase. In: Gotto AM (ed) Plasma lipoproteins. Elsevier, New York, pp 335–357

    Google Scholar 

  • Gruen R, Hietanen E, Greenwood MRC (1978) Increased adipose tissue lipoprotein lipase activity during the development of the genetically obese rat (fa/fa). Metabolism 27:1955–1966

    Google Scholar 

  • Hegele RA, Nakamura Y, Emi M, Lalouel JM, White R (1989) A BgIII RFLP at the lipoprotein lipase gene. Nucleic Acids Res 17:8899

    Google Scholar 

  • Heinzmann C, Ladias J, Antonarakis S, Kirchgessner T, Schotz MC, Lusis AJ (1987) RFLP for the human lipoprotein lipase (LPL) gene: HindIII. Nucleic Acids Res 15:6763

    Google Scholar 

  • Heinzmann C, Ladias J, Antonarakis S, Diep A, Schotz MC, Lusis AJ (1988) Two polymorphisms of the human hepatic lipase (HL) gene. Nucleic Acids Res 16:4739

    Google Scholar 

  • Heinzmann C, Clarke CF, Klisak I, Mohandas T, Sparkes RS, Edwards PA, Lusis AJ (1989) Dispersed family of human genes with sequence similarity to farnesyl pyrophosphate synthetase. Genomics 5:495–500

    Google Scholar 

  • Jackson RL (1983) Lipoprotein lipase and hepatic lipase. In: Boyer P (ed) The enzymes, vol 16. Academic Press, New York, pp 141–181

    Google Scholar 

  • Kirchgessner TG, Chuat JC, Heinzmann C, Etienne J, Guilhot S, Svenson K, Ameis D, Pilon C, d'Auroil L, Andalibi A, Schotz MC, Galibert F, Lusis AJ (1989) Organization of the human lipoprotein lipase gene and evolution of the lipase gene family. Proc Natl Acad Sci USA 86:9647–9651

    Google Scholar 

  • Komaromy MC, Schotz MC (1987) Cloning of rat hepatic lipase cDNA: evidence for a lipase gene family. Proc Natl Acad Sci USA 84:1526–1530

    Google Scholar 

  • Kuusi T, Ehnholm C, Viikari J, Harkonen R, Vartiainen E, Puska P, Taskinen MR (1989) Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia. J Lipid Res 340:1117–1126

    Google Scholar 

  • Kwiterovich PO Jr, White S, Forte T, Bachorik PS, Smith H, Sniderman A (1987) Hyperapobetalipoproteinemia in a kindred with familial combined hyperlipidemia and familial hypercholesterolemia. Arteriosclerosis 7:211–225

    Google Scholar 

  • Ladias JA, Kwiterovich PO, Smith HH, Miller M, Bachorik PS, Forte T, Lusis AJ, Antonarakis SE (1989) Apolipoprotein B-100 Hopkins (arginine4019-tryptophan). JAMA 262:1980–1988

    Google Scholar 

  • Langlois S, Deeb S, Bronzell JD, Kastelein JJ, Hayden MR (1989) A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency. Proc Natl Acad Sci USA 86:948–952

    Google Scholar 

  • Li S, Oka K, Galton D, Stocks J (1988) BstI RFLP at the human lipoprotein lipase (LPL) gene locus. Nucleic Acids Res 16: 2358

    Google Scholar 

  • Lipid Research Clinics Program (1974) Manual of laboratory operations: lipid and lipoprotein analysis. National Heart, Lung, and Blood Institute. Department of Health, Education and Welfare Publications (NIH) 75-628

  • Lithell H, Boberg J (1978) The lipoprotein-lipase activity of adipose tissue from different sites in obese women and relationship to all size. Int J Obes 2:47–52

    Google Scholar 

  • Lusis AJ (1988) Genetic factors affecting blood lipoproteins: the candidate gene approach. J Lipid Res 29:397–430

    Google Scholar 

  • Magill P, Rao SN, Miller NE, Nicoll A, Brunzell J, St. Hilaire J, Lewis B (1982) Relationships between the metabolism of high density and very low density lipoproteins in man: studies of apolipoprotein kinetics and adipose tissue lipoprotein lipase activity. Eur J Clin Invest 12:113–120

    Google Scholar 

  • Miller NE (1980) HDL cholesterol, tissue cholesterol, and coronary atherosclerosis: epidemiological correlations. In: Gotto AM Jr, Allen B (eds) Atherosclerosis. Springer, New York Berlin Heidelberg, pp 500–503

    Google Scholar 

  • Nikkila EA, Taskinen MR, Kekki M (1978) Relation of plasma high density lipoprotein cholesterol to lipoprotein lipase activity in adipose and skeletal muscle of man. Atherosclerosis 29: 497–501

    Google Scholar 

  • Nikkila EA, Kuusi T, Taskinen MR (1984) Regulation of lipoprotein metabolism by endothelial lipolytic systems. In: Carlson LA, Olsson AG (eds) Treatment of hyperlipoproteinemias. Raven Press, New York, pp 78–84

    Google Scholar 

  • Patsch JR, Gotto AM Jr, Olivecrona T, Eisenberg S (1978) Formation of high density lipoprotein 2-like particles from lipolysis of very low density lipoproteins in vitro. Proc Natl Acad Sci USA 75:4519–4523

    Google Scholar 

  • Sparkes RS, Zollman S, Klisak I, Kirchgessner TG, Komarom MC, Mohandas T, Schotz MC, Lusis AJ (1987) Human genes involved in lipolysis of plasma lipoproteins: mapping of loci for lipoprotein lipase to 8p22 and hepatic lipase to 15q21. Genomics 1:138–144

    Google Scholar 

  • Thompson EA, Deeb S, Walker D, Motulsky AG (1988) The detection of linkage disequilibrium between closely linked markers: RFLP's at the AI-CIII apolipoprotein genes. Am J Hum Genet 42:113–124

    Google Scholar 

  • Wion KL, Kirchgessner TG, Lusis AJ, Schotz MC, Lawn RM (1987) Human lipoprotein lipase complementary DNA sequence. Science 235:1638–1641

    Google Scholar 

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  1. Carol Derby

    Present address: Department of Epidemiology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, 10461, Bronx, NY, USA

Authors and Affiliations

  1. Department of Medicine and Department of Microbiology and Molecular Biology Institute, UCLA, 90024, Los Angeles, CA, USA

    Camilla Heizmann, Todd Kirchgessner & Aldons J. Lusis

  2. Department of Pediatrics and Center for Medical Genetics, The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA

    Peter O. Kwiterovich, John A. Ladias, Carol Derby & Stylianos E. Antonarakis

Authors
  1. Camilla Heizmann
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  2. Todd Kirchgessner
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  3. Peter O. Kwiterovich
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  4. John A. Ladias
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  5. Carol Derby
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  6. Stylianos E. Antonarakis
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  7. Aldons J. Lusis
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Heizmann, C., Kirchgessner, T., Kwiterovich, P.O. et al. DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels. Hum Genet 86, 578–584 (1991). https://doi.org/10.1007/BF00201544

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  • DOI: https://doi.org/10.1007/BF00201544

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