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:

Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Québec Family Study

International Journal of Obesity volume 25, pages 1332–1339 (2001)Cite this article

Abstract

OBJECTIVE: To investigate whether interactions between glucocorticoid receptor (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene markers contribute to individual differences in indicators of adiposity and abdominal obesity, including visceral fat level.

DESIGN AND SUBJECTS: Cross-sectional study; 742 individuals from the phase 2 of the Québec Family Study cohort.

MEASUREMENTS: Total body fat assessed by hydrodensitometry and the sum of six skinfolds. Abdominal fat areas measured by computed tomography and adjusted for age, sex and total fat mass in all analyses. GRL Bcl I, α2A-ADR Dra I and β2-ADR Ban I markers were typed by Southern blot, and other markers by polymerase chain reaction technique.

RESULTS: It is confirmed that the 4.5 kb allele of the GRL BclI polymorphism is associated with a higher amount of abdominal visceral fat (AVF) depot (P for trend<0.001) independent of the level of total body fat. Furthermore, the α2-ADR Dra I variant is associated with lower cross-sectional areas of abdominal total (P=0.003) and subcutaneous (P=0.012) adipose tissue. Gene–gene interactions between GRL and α2-ADR genes affecting overall adiposity (P=0.016) as well as between GRL and β2-ADR genes (P=0.049) having influence on total abdominal fat levels were observed. When the three genes were considered together in the same analysis, significant interactions having influence on overall adiposity (P=0.017), abdominal total (P=0.032) and visceral fat (P=0.002) were observed. About 1–2% of the total variation in total fatness and abdominal fat was explained by these gene–gene interactions.

CONCLUSION: There is an association between the GRL BclI polymorphism and increased AVF levels independent of the level of total body fat. The α2-ADR DraI variant is associated with a lower cross-sectional area of abdominal total fat. Numerous interactions between GRL and ADR markers on overall adiposity and total abdominal fat as well as between GRL, LPL and ADR genes on overall adiposity, abdominal total and visceral fat suggest that the genetic architecture of body fat content and adipose tissue distribution is complex although some genes, like GRL, may have ubiquitous effects.

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

Similar content being viewed by others

References

  1. Bouchard C, Després J-P, Mauriége P . Genetic and nongenetic determinants of regional fat distribution Endocr Rev 1993 14: 72–93.

    Article  CAS  Google Scholar 

  2. Eckel RH . Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. New Engl J Med 1989 320: 1060–1068.

    Article  CAS  Google Scholar 

  3. Fain JN, Garcia-Sainz JA . Adrenergic regulation of adipocyte metabolism J Lipid Res 1983 24: 945–966.

    CAS  PubMed  Google Scholar 

  4. Cigolini M, Smith U . Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effects of glucocorticoids. Metabolism 1979 28: 502–510.

    Article  CAS  Google Scholar 

  5. Bamberger CM, Schulte HM, Chrousos GP . Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids Endocr Rev 1996 17: 245–261.

    Article  CAS  Google Scholar 

  6. Gagnon J, Mauriége P, Roy S, Sjostrom D, Chagnon YC, Dionne FT, Oppert JM, Pérusse L, Sjostrom L, Bouchard C . The Trp64Arg mutation of the β3 adrenergic receptor gene has no effect on obesity phenotypes in the Québec Family Study and Swedish Obese Subjects cohorts J Clin Invest 1996 98: 2086–2093.

    Article  CAS  Google Scholar 

  7. Buemann B, Vohl M-C, Chagnon M, Chagnon YC, Gagnon J, Pérusse L, Dionne F, Després J-P, Tremblay A, Nadeau A, Bouchard C . Abdominal visceral fat is associated with a Bcl I restriction fragment length polymorphism at the glucocorticoid receptor gene locus Obes Res 1997 5: 186–192.

    Article  CAS  Google Scholar 

  8. Bouchard C . Genetics of obesity: overview and research directions. In: Bouchard C (ed). The genetics of obesity CRC Press: Boca Raton, FL 1994 223–233.

    Google Scholar 

  9. Theriault A, Boyd E, Harrap SB, Hollenberg SM, Connor JM . Regional chromosomal assignment of the human glucocorticoid receptor gene to 5q31 Hum Genet 1989 83: 289–291.

    Article  CAS  Google Scholar 

  10. Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RA, Keller P, Caron MG, Lefkowitz RJ . Delineation of the intronless nature of the genes for the human and hamster β2-adrenergic receptor and their putative promoter region J Biol Chem 1987 262: 7321–7327.

    CAS  PubMed  Google Scholar 

  11. Bouchard C . Genetic epidemiology, association and sib-pair linkage: results from the Québec Family Study. In: Bray GA, Ryan DH (eds). Molecular and genetic aspects of obesity Vol 5: Pennington Center Nutrition Series, Louisiana State University Press: Baton Rouge, LA 1996 470–481.

    Google Scholar 

  12. Behnke AR, Wilmore JH (eds) . Evaluation and regulation of body build and composition Prentice-Hall: Englewood Cliffs, NJ 1974 20–37.

    Google Scholar 

  13. Siri WE . The gross composition of the body. In: Lawrence JH, Tobias CA (eds). Advances in biological and medical physics Vol 4: Academic Press: NewYork 1956 239–280.

    Google Scholar 

  14. Meneely GR, Kaltreider NL . The volume of the lung determined by helium dilution: description of the method and comparison with other procedures J Clin Invest 1949 28: 129–139.

    Article  CAS  Google Scholar 

  15. Weiner JS, Lourie JA (eds) . Human biology: a guide to field methods Blackwell: Oxford 1969.

    Google Scholar 

  16. Ferland M, Després JP, Tremblay A, Pinault S, Nadeau A, Moorjani S, Lupien PJ, Theriault G, Bouchard C . Assesment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements Br J Nutr 1989 61: 139–148.

    Article  CAS  Google Scholar 

  17. Neitzel H . A routine method for the establishment of permanent growing lymphoblastoid cell lines Hum Genet 1986 73: 320–326.

    Article  CAS  Google Scholar 

  18. Large V, Hellstrom L, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  Google Scholar 

  19. Hata A, Robertson M, Emi M, Lalouel JM . Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene Nucleic Acids Res 1990 18: 5407–5411.

    Article  CAS  Google Scholar 

  20. Garenc C, Pérusse L, Gagnon J, Chagnon YC, Bergeron J, Després J-P, Province MA, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C . Linkage and association studies of the lipoprotein lipase gene with post-heparin plasma lipase activities, body fat and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study Metabolism 2000 49: 432–439.

    Article  CAS  Google Scholar 

  21. Hollenberg SM, Weinberg C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfed MG, Evans RM . Primary structure and expression of a functional human glucocorticoid receptor cDNA Nature 1985 318: 635–641.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Pérusse L, Chagnon YC, Després J-P, Bouchard C . Interactions among the α2-, β2- and β3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study Metabolism 2000 49: 1063–1070.

    Article  CAS  Google Scholar 

  24. Weaver JU, Hitman GA, Kopelman PG . An association between a BclI restriction fragment length polymorphism of the glucocorticoid receptor locus and hyperinsulinaemia in obese women J Mol Endocrinol 1992 9: 295–300.

    Article  CAS  Google Scholar 

  25. Clément K, Philippi A, Jury C, Pividal R, Hager J, Demenais F, Basdevant A, Guy-Grand B, Froguel P . Candidate gene approach of familial morbid obesity: linkage analysis of the glucocorticoid receptor gene Int J Obes Relat Metab Disord 1996 20: 507–512.

    PubMed  Google Scholar 

  26. Takami S, Wong ZYH, Stebbing M, Harrap SB . Linkage analysis of glucocorticoid and β2-adrenergic receptor genes with blood pressure and body mass index Am J Physiol 1999 276: H1379–H1384.

    CAS  PubMed  Google Scholar 

  27. Rebuffé-Scrive M, Lundholm K, Bjorntorp P . Glucocorticoid hormone binding to human adipose tissue Eur J Clin Invest 1985 15: 267–271.

    Article  Google Scholar 

  28. Panarelli M, Holloway CD, Fraser R, Connell JMC, Ingram MC, Anderson NH, Kenyon CJ . Glucocorticoid receptor polymorphism, skin vasoconstriction, and other metabolic intermediate phenotypes in normal human subjects J Clin Endocrinol Metab 1998 83: 1846–1852.

    CAS  PubMed  Google Scholar 

  29. Large V, Hellstrom L, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  Google Scholar 

  30. Green SA, Turki J, Innis M, Liggett SB . Aminoterminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties Biochemistry 1994 33: 9414–9419.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Medical Research Council of Canada (PG-11811, MT-13960, GR-15187), the Finnish Cultural Foundation and Medical Council of the Academy of Finland, and the Pennington Biomedical Research Center. We thank Monique Chagnon, ART, for her technical assistance. C Bouchard is supported in part by the George A Bray Chair in Nutrition.

Author information

Authors and Affiliations

  1. Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

    O Ukkola & C Bouchard

  2. Department of Internal Medicine, University of Oulu, Oulu, Finland

    O Ukkola

  3. Division of Kinesiology, Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Québec, Canada

    L Pérusse & YC Chagnon

  4. Lipid Research Center, Laval University, Ste-Foy, Québec, Canada

    J-P Després

Authors
  1. O Ukkola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Pérusse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. YC Chagnon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J-P Després
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Bouchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Bouchard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ukkola, O., Pérusse, L., Chagnon, Y. et al. Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Québec Family Study. Int J Obes 25, 1332–1339 (2001). https://doi.org/10.1038/sj.ijo.0801735

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801735

Keywords

This article is cited by

Search

Advanced search

Quick links