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 between β-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study

International Journal of Obesity volume 29, pages 746–754 (2005)Cite this article

Abstract

OBJECTIVES:

The β-adrenergic receptor (βAR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the β1AR (ADRB1), β2AR (ADRB2), β3AR (ADRB3), Gs protein alpha (GNAS1), to which all three β-receptors couple and the G protein β3 subunit (GNB3), to which β3ARs couple.

DESIGN:

A case–control genetic association study.

SUBJECTS:

A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation (WISE) study.

MEASUREMENTS:

Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made.

RESULTS:

Polymorphisms in the three βAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity.

CONCLUSIONS:

Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the βARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women.

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

Similar content being viewed by others

References

  1. Burton BT, Foster WR, Hirsch J, Van Itallie TB . Health implications of obesity: an NIH consensus development conference. Int J Obes Relat Metab Disord 1985; 9: 155–170.

    CAS  Google Scholar 

  2. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS . Obesity and the risk of heart failure. N Engl J Med 2002; 347: 305–313.

    Article  PubMed  Google Scholar 

  3. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ . Overweight, obesity and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348: 1625–1638.

    Article  PubMed  Google Scholar 

  4. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW . Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097–1105.

    Article  CAS  PubMed  Google Scholar 

  5. CDC, National Center for Health Statistics, National Health & Nutrition Examination Survey. Health, United States (Table 70) 2002. Available from URL: http://www.cdc.gov/nchs/products/pubs/pubd/hus/02tables.htm [Accessed 2004 Apr 3].

  6. Kushner RF . Medical management of obesity. Semin Gastrointest Dis 2002; 13: 123–132.

    PubMed  Google Scholar 

  7. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE . The body-mass index of twins who have been reared apart. N Engl J Med 1990; 322: 1483–1487.

    Article  CAS  PubMed  Google Scholar 

  8. Ravussin E, Bouchard C . Human genomics and obesity: finding appropriate drug targets. Eur J Pharmacol 2000; 410: 131–145.

    Article  CAS  PubMed  Google Scholar 

  9. Barbe P, Millet L, Galitzki J, Lafonatan M, Berlan M . In situ assessment of the role of β1-, β2-, and β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue. Br J Pharmacol 1996; 117: 907–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Haffner CA, Kendall MJ, Maxwell S, Hughes B . The lipolytic effect of β1- and β2-adrenoceptor activation in healthy human volunteers. Br J Clin Pharmacol 1993; 35: 35–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maqbool A, Hall AS, Ball SG, Balmforth AJ . Common polymorphisms of β1-adrenoceptor: identification and rapid screening assay [letter]. Lancet 1999; 353: 897.

    Article  CAS  PubMed  Google Scholar 

  12. Rathz DA, Brown KM, Kramer LA, Liggett SB . Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking. J Cardiovasc Pharmacol 2002; 39: 155–160.

    Article  CAS  PubMed  Google Scholar 

  13. Liggett SB . Polymorphisms of the β2-adrenergic receptor and asthma. Am J Resp Crit Care Med 1997; 156: S156–S162.

    Article  CAS  PubMed  Google Scholar 

  14. Lowe Jr WL, Rotimi CN, Luke A, Guo X, Zhu X, Comuzzie AG, Schuh TS, Halbach S, Kotlar TJ, Cooper RS . The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans. Int J Obes Relat Metab Disord 2001; 25: 54–60.

    Article  CAS  PubMed  Google Scholar 

  15. Waltman C, Levine MA, Schwindinger WF, Wand GS . Polymorphism of the gene encoding the alpha subunit of the stimulatory G-protein of adenylyl cyclase (GNAS1). Hum Genet 1994; 93: 477–478.

    Article  CAS  PubMed  Google Scholar 

  16. Gutersohn A, Naber C, Muller N, Erbel R, Siffert W . G protein β3 subunit 825TT genotype and post-pregnancy weight retenion. Lancet 2000; 355: 1240–1241.

    Article  CAS  PubMed  Google Scholar 

  17. Hauner H, Rohrig K, Siffert W . Effects of the G-protein β3 subunit 825T allele on adipogenesis and lipolysis in cultured human preadipocytes and adipocytes. Horm Metab Res 2002; 34: 475–480.

    Article  CAS  PubMed  Google Scholar 

  18. Large V, Hellström L, Reynisdottir S, Lönnqvist 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  PubMed  PubMed Central  Google Scholar 

  19. Drysdale CM, McGraw DW, Stack CB, Stephens JC, Judson RS, Nandabalan K, Arnold K, Ruano G, Liggett SB . Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000; 97: 10483–10488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bairey Merz N, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G . The Women’s Ischemia Syndrome Evaluation (WISE) Study: protocol design, methodology and feasibility report. J Am Coll Cardiol 1999; 33: 1453–1461.

    Article  Google Scholar 

  21. Bairey Merz N, Olson M, McGorray S, Pakstis DL, Zell K, Rickens CR, Kelsey SF, Bittner V, Sharaf BL, Sopko G . Physical activity and functional capacity measurement in women: a report from the NHLBI-sponsored WISE study. J Womens Health Gend Based Med 2000; 9: 769–777.

    Article  CAS  PubMed  Google Scholar 

  22. Lewontin RC . The interaction of selection and linkage. I. General considerations; heterotic models. Genetics 1964; 49: 49–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Pritchard JK, Przeworski SJ . Linkage disequilibrium in humans: models and data. Am J Hum Genet 2001; 69: 1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. World Health Organization. 1997 Obesity, preventing and managing the global epidemic. WHO: Geneva.

  25. Fujisawa T, Ikegami H, Kawaguchi Y, Ogihara T . Meta-analysis of the association of Trp64Arg polymorphism of beta-3-adrenergic receptor gene with body mass index. J Clin Endocrin Metab 1998; 83: 2441–2444.

    CAS  Google Scholar 

  26. Allison DB, Heo M, Faith MS, Pietrobelli A . Meta-analysis of the association of the Tyrp64Arg polymorphism in the beta 3-adrenergic receptor with body mass index. Int J Obes Relat Metab Disord 1998; 22: 559–566.

    Article  CAS  PubMed  Google Scholar 

  27. Schiffelers SLH, Saris WHM, Boomsma F, van Baak MA . β1- and β2-adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 2001; 86: 2191–2199.

    CAS  PubMed  Google Scholar 

  28. Macho-Azcarate T, Marti A, Gonzalez A, Martinez JA, Ibanez J . Gln27Glu polymorphism in the β2-adrenergic receptor gene and lipid metabolism during exercise in obese women. Int J Obes Relat Metab Disord 2002; 26: 1434–1441.

    Article  CAS  PubMed  Google Scholar 

  29. Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K . Association of polymorphisms in the β2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 1999; 42: 98–101.

    Article  CAS  PubMed  Google Scholar 

  30. Oberkofler H, Esterbauer H, Hell E, Krempler F, Patsch W . The Gln27Glu polymorphism in the β2-adrenergic receptor gene is not associated with morbid obesity in Austrian women. Int J Obes Relat Metab Disord 2000; 24: 388–390.

    Article  CAS  PubMed  Google Scholar 

  31. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P . Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population. Int J Obes Relat Metab Disord 2000; 24: 382–387.

    Article  CAS  PubMed  Google Scholar 

  32. Moriarty M, Wing RR, Kuller LH, Ferrell RE . Trp64Arg substitution in the beta 3-adrenergic receptor does not relate to body weight in healthy premenopausal women. Int J Obes Relat Metab Disord 1997; 21: 826–829.

    Article  CAS  PubMed  Google Scholar 

  33. Elbein SC, Hoffman M, Barrett K, Wegner K, Miles C, Bachman K, Berkowitz D, Shuldiner AR, Leppert MF, Hasstedt S . Role of the β3-adrenergic receptor locus in obesity and noninsulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair. J Clin Endocrinol Metab 1996; 81: 4422–4427.

    CAS  PubMed  Google Scholar 

  34. Dionne IJ, Garant MJ, Nolan AA, Pollin TI, Lewis DG, Shuldiner AR, Poehlman ET . Association between obesity and a polymorphism in the β1-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women. Int J Obes Relat Metab Disord 2002; 26: 633–639.

    Article  CAS  PubMed  Google Scholar 

  35. Ellsworth DL, Coady SA, Chen W, Srinivasan SR, Elkasabany A, Gustat J, Boerwinkle E, Berenson GS . Influence of the β2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 2002; 26: 928–937.

    Article  CAS  PubMed  Google Scholar 

  36. Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF . Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther 2003; 74: 44–52.

    Article  CAS  PubMed  Google Scholar 

  37. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P . β2-Adrenoceptor gene polymorphism, body weight, and physical activity. Lancet 1999; 353: 896.

    Article  CAS  PubMed  Google Scholar 

  38. del Moral AM, Corbalán MS, Martínez-Gonzalez A, Martinez JA . TRP64ARG polymorphism of the β3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle. Diabetes, Obes Metab 2002; 4: 428–430.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH Grants R03HL65729, U01-HL64924-01, and Orchid Biosciences, Inc. The WISE study is supported by Grants N01-HV68161, N01-HV68162, N01-HV68163, N01-HV68164 from the National Institutes of Health, Grant M01-RR00425 from the National Center for Research Resources; Grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey; the Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; and the Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania. Dr Terra was an American Foundation for Pharmaceutical Education (Rockville, Maryland) Clinical Pharmacy Post-Pharm.D. Fellow in the Biomedical Research Sciences at the time of this work.

Author information

Authors and Affiliations

  1. Department of Pharmacy Practice, University of Florida College of Pharmacy, Gainesville, FL, USA

    S G Terra, L H Cavallari & J A Johnson

  2. Department of Statistics, University of Florida, Gainesville, FL, USA

    S P McGorray & R Wu

  3. Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    D M McNamara

  4. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA

    L H Cavallari

  5. Orchid Biosciences Inc., Princeton, NJ, USA

    J R Walker

  6. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA

    M R Wallace

  7. Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA

    M R Wallace

  8. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    B D Johnson

  9. Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    C N Bairey Merz

  10. Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, Bethesda, MD, USA

    G Sopko

  11. Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL, USA

    C J Pepine & J A Johnson

Authors
  1. S G Terra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S P McGorray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D M McNamara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L H Cavallari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J R Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M R Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B D Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C N Bairey Merz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Sopko
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C J Pepine
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J A Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J A Johnson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Terra, S., McGorray, S., Wu, R. et al. Association between β-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study. Int J Obes 29, 746–754 (2005). https://doi.org/10.1038/sj.ijo.0802978

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802978

Keywords

This article is cited by

Search

Advanced search

Quick links