Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Association of sets of alleles of genes encoding β3–adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity

International Journal of Obesity volume 24, pages 93–100 (2000)Cite this article

Abstract

OBJECTIVE: To investigate the relationship between the polymorphisms of the β3–AR (Trp64Arg), UCP1 (A→G) and LPL (HindIII and PvuII) loci and the metabolic complications associated with obesity in a Turkish population.

SUBJECTS: 271 unrelated individuals of Turkish origin including obese (body mass index, BMI>30 kg/m2) and lean (BMI≤25 kg/m2) subjects.

MEASUREMENTS: Anthropometric (weight, height and blood pressure) and metabolic measurements (plasma levels of glucose, cholesterol and triglycerides), and determination of β3–AR, UCP1 and LPL genotypes by polymerase chain reaction followed by enzymatic digestion.

RESULTS: The distributions of genotypes for each candidate gene (β3–AR, UCP1 and LPL) were similar between the obese and the lean subjects. The Arg64 allele of the β3–AR gene was absent from massively obese men. GG carriers of the A→G variant of the UCP1 gene showed BMI-associated increases of cholesterol levels which were more marked than both AA (P=0.027) and AG (P=0.039) carriers. Obese P+ carriers of the LPL PvuII variant had significantly higher levels of glucose than non-carriers (P=0.011), whereas obese P+P+ carriers did not have significantly different levels of triglycerides than non-carriers (P=0.087). Moreover, carriers of both alleles (G&P+) had higher levels of glucose than non-carriers (P=0.048), but did not have significantly different levels of triglycerides than non-carriers (P=0.125). However, the BMI-associated increase of triglycerides of P+&G carriers was significantly more marked than that of P+ carriers (P=0.0085).

CONCLUSION: Our data support the idea that alleles of specific genes (UCP1, LPL and β3–AR) might play a role in the development of certain metabolic complications of obesity and might have additive effects when combined with each other (as in the case of UCP1 and LPL).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Vohl MC, Lamarche B, Moorjani S, Prud'homme D, Nadeau A, Bouchard C Lupien PJ, Despré JP . The lipoprotein lipase HindIII polymorphism modulates plasma triglyceride levels in visceral obesity Arterioscler Thromb Vasc Biol 1995 15: 714–720.

    Article  CAS  Google Scholar 

  2. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue Nature 1994 372: 425–432.

    Article  CAS  Google Scholar 

  3. Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, Manning BS, Strosberg AD, Stern MP, Raben N, Sorkin JD, Roth J, Shuldiner A . Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene New Engl J Med 1995 333: 343–347.

    Article  CAS  Google Scholar 

  4. Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD . Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity New Engl J Med 1995 333: 352–354.

    Article  Google Scholar 

  5. Kadowaki R, Yasuda K, Iwamoto K, Otabe S, Shimokawa K, Silver K, Walston J, Yoshinaga H, Kosaka Y, Yamada N, Saito Y, Hagura R, Akanuma Y, Shuldiner A, Yazaki Y, Kadowaki T . A mutation in the β3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects Biochem Biophys Res Commun 1995 215: 555–560.

    Article  CAS  Google Scholar 

  6. Widén E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC . Association of a polymorphism in the β3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns New Engl J Med 1995 333: 348–351.

    Article  Google Scholar 

  7. Strosberg AD . Association of β3-adrenoreceptor polymorphism with obesity and diabetes: Current status Trends Pharmac Sci 1997 18: 449–454.

    Article  CAS  Google Scholar 

  8. Clément K, Ruiz J, Cassard-Doulcier AM, Bouillaud F, Ricquier D, Basdevant A, Guy-Grand B, Froguel P . Additive effect of A→G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the β3-adrenergic receptor gene on weight gain in morbid obesity Int J Obes 1996 20: 1062–1066.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Wang XL, McCredie RM, Wilcken DEL . Common DNA polymorphism at the lipoprotein lipase gene. Association with severity of coronary artery disease and diabetes Circulation 1996 93: 1339–1345.

    Article  CAS  Google Scholar 

  11. Palou A, Pico C, Bonet ML, Oliver P . Molecules in focus: Uncoupling protein Int J Biochem Cell Biol 1998 30: 7–11.

    Article  CAS  Google Scholar 

  12. Anderson KM, Kannel WB . Obesity and disease. In Björntorp P, Brodoff BN (eds) Obesity. Lippincott: Philadelphia, PA 1992 pp 465–473.

    Google Scholar 

  13. Mahley RW, Palaoglu KE, Atak Z, Dawson-Pepin J, Langlois AM, Cheung V, Onat H, Fulks P, Mahley LL, Vakar F, OzbayrakçI S, Gökdemir O, Winkler W . Turkish heart study: Lipids, lipoproteins, and apolipoproteins J Lipid Res 1995 36: 839–859.

    CAS  PubMed  Google Scholar 

  14. National Diabetes Data group . Classification of diabetes mellitus and other categories of glucose intolerance Diabetes 1979 28: 1039–1057.

    Article  Google Scholar 

  15. Trinder P . Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor Ann Clin Biochem 1969 69: 24–27.

    Article  Google Scholar 

  16. Barham D, Trinder P . An improved colour reagent for the determination of blood glucose by the oxidase system Analyst 1972 97: 142–145.

    Article  CAS  Google Scholar 

  17. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC . Enzymatic determination of total serum cholesterol Clin Chem 1974 20: 470–475.

    CAS  PubMed  Google Scholar 

  18. Bucolo G, David H . Quantitative determination of serum triglycerides by the use of enzymes Clin Chem 1973 19: 476–482.

    CAS  PubMed  Google Scholar 

  19. Megraw RE, Dunn DE, Biggs HG . Manual and continuous-flow colorimetry of triacylglycerols by a fully enzymic method Clin Chem 1979 25: 273–278.

    CAS  PubMed  Google Scholar 

  20. Sambrook J, Fritsch EF, Maniatis T . In Molecular cloning, 2nd ed. Cold Spring Harbor Laboratory Press: Cold Spring Harbor 1989 9.14–9.23.

  21. Cassard-doulcier AM, Bouillaud F, Chagnon M, Gelly C, Dionne FT, Oppert JM, Bouchard C, Chagnon Y, Ricquier D . The BclI polymorphism of the human uncoupling protein (UCP) gene is due to a point mutation in the 5′–flanking region Int J Obes 1996 20: 278–279.

    CAS  Google Scholar 

  22. Ahn YI, Kamboh MI, Hamman RF, Cole SA, Ferrell RE . Two DNA polymorphisms in the lipoprotein lipase gene and their associations with factors related to cardiovascular disease J Lipid Res 1993 34: 421–428.

    CAS  PubMed  Google Scholar 

  23. Togan I, Ergüven A . Red cell enzyme and blood group polymorphisms in Turkey Gene Geog 1994 8: 75–80.

    CAS  Google Scholar 

  24. Gerdes C, Gerdes LU, Hansen PS, Faergeman O . Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men Circulation 1995 92: 1765–1769.

    Article  CAS  Google Scholar 

  25. Jemaa R, Tuzet S, Portos C, Betoulle D, Apfelbaum M, Fumeron F . Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and body mass index in obese people Int J Obes 1995 19: 270–274.

    CAS  Google Scholar 

  26. Lonnqvist F, Thorne A, Nilsell K, Hoffstedt J, Arner P . A pathogenic role of visceral fat β3-adrenoceptors in obesity J Clin Invest 1995 95: 1109–1116.

    Article  CAS  Google Scholar 

  27. Lonnqvist F, Thorne A, Large V, Arner P . Sex differences in visceral fat lipolysis and metabolic complications of obesity Arteriorscler. Thromb. Vasc. Biol. 1997 17 (7): 1472–1480.

    Article  CAS  Google Scholar 

  28. Willett WC, Manson JE, Stampfer MJ, Colditz GA, Rosner B, Speizer FE, Hennekens CH . Weight, weight change and coronary heart disease in women: Risk within the normal weight range JAMA 1995 273 (6): 461–465.

    Article  CAS  Google Scholar 

  29. Borkan GA, Sparrow D, Wisniewski C, Vokonas PS . Body weight and coronary disease risk: Patterns of risk factor change associated with long-term weight change. The Normative Ageing Study Am J Epidemiol 1986 124: 410–419.

    Article  CAS  Google Scholar 

  30. Anderson KM, Wilson PW, Garrison RJ, Castelli WP . Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample Atherosclerosis 1987 68: 59–66.

    Article  CAS  Google Scholar 

  31. Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjostrom L . Distribution of adipose tissue and risk of cardiovascular disease and death: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden Br Med J 1984 289: 1257–1261.

    Article  CAS  Google Scholar 

  32. Caro J . Insulin resistance in obese and non obese man J Clin Endocrinol Metab 1990 73: 691–695.

    Article  Google Scholar 

  33. Mitchell RJ, Earl L, Bray P, Fripp YJ, Williams J . DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides Human Biol 1994 66: 383–397.

    CAS  PubMed  Google Scholar 

  34. Despres JP, Moorjani S, Lupien P-J, Tremblay A, Nadeau A, Bouchard C . Genetic aspects of susceptibility to obesity and related dyslipidemias Mol Cell Biochem 1992 113: 151–169.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut Cochin de Génétique Moléculaire, Laboratoire d'ImmunoPharmacologie Moléculaire, CNRS UPR 0415 and Université de Paris VII 22, rue Méchain, Paris, 75014, France

    AM Proenza, CM Poissonnet & AD Strosberg

  2. Departmenta Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Cra. Valldemossa, km 7,5, Palma de Mallorca, 07071, Spain

    AM Proenza & A Palou

  3. Department of Endocrinology and Metabolism, Gulhäne School of Medicine, Etlik-Ankara, Turkey

    M Ozata

  4. Department of Medical Biology, Gulhäne School of Medicine, Etlik-Ankara, Turkey

    S Ozen & S Guran

Authors
  1. AM Proenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. CM Poissonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Ozata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Ozen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Guran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Palou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. AD Strosberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to AD Strosberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Proenza, A., Poissonnet, C., Ozata, M. et al. Association of sets of alleles of genes encoding β3–adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity. Int J Obes 24, 93–100 (2000). https://doi.org/10.1038/sj.ijo.0801091

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801091

Keywords

This article is cited by

Search

Advanced search

Quick links