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.

  • Original Article
  • Published:

Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy

European Journal of Clinical Nutrition volume 61, pages 1213–1219 (2007)Cite this article

Abstract

Objective:

To evaluate the prevalence of β3-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity.

Design:

Cross-sectional outpatients study.

Patients and methods:

In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method.

Results:

Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (β=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects.

Conclusion:

We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.

Sponsorship:

MIUR, COFIN 2004.

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

Similar content being viewed by others

References

  • Adams TD, Hunt SC, Mason LA, Ramirez ME, Fisher AG, Williams RR (1993). Familial aggregation of morbid obesity. Obes Res 1, 261–270.

    Article  CAS  Google Scholar 

  • Afonina IA, Zivarts M, Kutyavin IV, Lukhtanov EA, Gamper H, Meyer RB (1997). Efficient priming of PCR with short oligonucleotides conjugated to a minor groove binder. Nucleic Acids Res 25, 2657–2660.

    Article  CAS  Google Scholar 

  • Allison DB, Heo M, Faith MS, Pietrobelli A (1998). Meta-analysis of the association of the Trp64Arg polymorphism in the beta 3-adrenergic receptor with body mass index. Int J Obes Relat Metab Disord 22, 559–566.

    Article  CAS  Google Scholar 

  • Arch JRS, Kaumann AJ (1993). β3 and atypical β-adrenoceptors. Med Res Rev 13, 663–729.

    Article  CAS  Google Scholar 

  • Arner P (2000). Hunting for human obesity genes? Look in the adipose tissue. Int J Obes Relat Metab Disorder 24, S57–S62.

    Article  CAS  Google Scholar 

  • Astrup A, Raben A, Buemann B, Toubro S (1997). Fat metabolism in the prediction to obesity. Ann NY Acad Sci 827, 417–428.

    Article  CAS  Google Scholar 

  • Awata T, Katayama S (1996). Genetic variation in the β3-adrenergic receptor in Japanese NIDDM patients. Diabet Care 19, 271–272.

    Article  CAS  Google Scholar 

  • Candelore MR, Deng L, Tota LM, Kelly LJ, Cascieri MA, Strader D (1996). Pharmacological characterization of a recently described human β3-adrenergic receptors in obesity. Endocrinology 137, 2638–2641.

    Article  CAS  Google Scholar 

  • Clement K, Vaisse C, Manning BJ, Basdevant A, Guy-Grand B, Ruiz J et al. (1995). Genetic variation in the β3-adrenergic receptor and an increase capacity to gain weight in patient with morbid obesity. N Engl J Med 333, 352–354.

    Article  CAS  Google Scholar 

  • Corella D, Guillén M, Portolés O, Sorlì JV, Alonso V, Folch J et al. (2001). Gender specific associations of the Trp64Arg mutation in the β3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. Int J Obes Relat Metab Disord 25, 348–360.

    Google Scholar 

  • Evans D, Minouchher S, Hagemann G, Mann WA, Wendt D, Wolf A et al. (2000). Frequency of and interaction between polymorphisms in the β3-adrenergic receptor and in uncoupling proteins 1 and 2 and obesity in Germans. Int J Obes Relat Metab Disord 24, 1239–1245.

    Article  CAS  Google Scholar 

  • Flegal KM, Carroll MD, Ogden CL (2002). Prevalance and trends in obesity among US adults, 1999–2000. JAMA 288, 1723–1727.

    Article  Google Scholar 

  • Friedewald WT, Levy RI, Frederickson DS (1972). Estimation of the concentration of low density lipoprotein in plasma without use of a preparative ultracentrifuge. Clin Chem 18, 449–456.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Gagnon J, Mauriege P, Roy S, Sjostrom D, Chagnon YC, Dionne FT et al. (1996). The Trp64Arg mutation of the β3-adrenergic receptor gene has no effect on obesity phenotypes in the Quebec family study and Swedish obese subjects cohorts. J Clin Invest 98, 2086–2093.

    Article  CAS  Google Scholar 

  • Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. (2005). Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation 25, 2735–2752.

    Article  Google Scholar 

  • Hoffstedt L, Poirier O, Thörne A, Lönnqvist F, Herrmann SM, Cambien F et al. (1999). Polymorphism of the human β3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function. Diabetes 48, 203–205.

    Article  CAS  Google Scholar 

  • Kadowaki H, Yasuda K, Iwamoto K, Otabe S, Shimokawa K, Silver K et al. (1995). A mutation in the β3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects. Biochem Biophys Res Commun 215, 555–560.

    Article  CAS  Google Scholar 

  • Katzmarzyk P, Perusse L, Bouchard C (1999). Genetics of abdominal visceral fat levels. Am J Hum Biol 11, 225–235.

    Article  Google Scholar 

  • Krief S, Lönnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P et al. (1993). Tissue distribution of β3-adrenergic receptor mRNA in man. J Clin Invest 91, 344–349.

    Article  CAS  Google Scholar 

  • Kurokawa N, Nakai K, Kameo S, Liu ZM, Satoh H (2001). Association of BMI with the β3-adrenergic receptor gene polymorphism in Japanese: meta-analysis. Obes Res 9, 741–745.

    Article  CAS  Google Scholar 

  • Kutyavin IV, Afonina IA, Mills A, Gorn VV, Lukhtanov EA, Belousov ES et al. (2000). 3′-minor groove binder-DNA probes increase sequence specificity at PCR extention temperatures. Nucleic Acids Res 28, 655–661.

    Article  CAS  Google Scholar 

  • Livak KJ (1999). Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal Biomol E 14, 143–149.

    Article  CAS  Google Scholar 

  • Lofontan M, Berlan M (1993). Fat cell adrenergic receptors and the control of white and brown fat cell function. J Lipid Res 34, 1057–1091.

    Google Scholar 

  • Lönnqvist F, Krief S, Strsberg AD, Nyberg S, Emorine LJ, Amer P (1995). A pathogenic role of visceral fat β3-adrenoceptors in obesity. J Clin Invest 95, 1109–1116.

    Article  Google Scholar 

  • Luke A, Durazo-Arvizu R, Rotimi C, Prewitt TE, Ferrester T, Wilks R et al. (1997). Relation between body mass index and body fat in black population samples from Nigeria, Jamaica and the United States. Am J Epidemiol 145, 620–628.

    Article  CAS  Google Scholar 

  • Marra M, Scalfi L, Contaldo F, Pasanisi F (2004). Fasting respiratory quotient as a predictor of long-term weight changes in non-obese women. Ann Nutr Metab 48, 189–192.

    Article  CAS  Google Scholar 

  • Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC et al. (1985). Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419.

    Article  CAS  Google Scholar 

  • Moriarty M, Wing RR, Kuller LH, Ferrel RE (1997). Trp64Arg substitution in the b3-adrenergic receptor does not relate to body weight in healthy, premenopausal women. Int J Obes Relat Metab Disord 21, 829.

    Article  Google Scholar 

  • Oksanen L, Mustajoki P, Kaprio J, Kainulainen K, Janne O, Peltonen L et al. (1996). Polymorphism of the β3-adrenergic receptor gene in morbid obesity. Int J Obes 20, 1055–1061.

    CAS  Google Scholar 

  • Perfetti R, Hui H, Chamie K, Binder S, Seibert M, McLenithan J et al. (2001). Pancreatic beta-cells expressing the Arg64 variant of the beta(3)-adrenergic receptor exhibit abnormal insulin secretory activity. J Mol Endocrinol 27, 133–144.

    Article  CAS  Google Scholar 

  • Pietri-Rouxel F, Manning BSTJ, Gros J, Strosberg AD (1997). The biochemical effect of the naturally occurring Trp64Arg mutation on human β3-adrenoceptor activity. Eur J Biochem 247, 1174–1179.

    Article  CAS  Google Scholar 

  • Price RA, Ness R, Laskarzewski P (1990). Common major gene inheritance of extreme overweight. Hum Biol 62, 747–765.

    CAS  PubMed  Google Scholar 

  • Seals DR, Bell C (2004). Chronic sympathetic activation: consequence and cause of age-associated obesity? Diabetes 53, 276–284.

    Article  CAS  Google Scholar 

  • Seidell JC, Muller DC, Sorkin JD, Andres R (1992). Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore longitudinal study. Int J Obes 16, 667–674.

    CAS  Google Scholar 

  • Shiwaku K, Gao TQ, Isobe A, Fukushima T, Yamane Y (1998). A Trp64Arg mutation in the β3-adrenergic receptor gene is not associated with moderate overweight in Japanese workers. Metabolism 47, 1528–1530.

    Article  CAS  Google Scholar 

  • Snitker S, Odeleye OE, Hellmer J, Boschmann M, Monroe MB, Shuldiner AR et al. (1997). No effect of the Trp64Arg β3-adrenoceptor variant on in vivo lipolysis in subcutaneous tissue. Diabetologia 40, 838–842.

    Article  CAS  Google Scholar 

  • Strazzullo P, Iacone R, Siani A, Cappuccio FP, Russo O, Barba G et al. (2001). Relationship of Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure: interaction with age. Cross-sectional and longitudinal findings of the Olivetti prospective heart study. J Hypertens 19, 399–406.

    Article  CAS  Google Scholar 

  • Thomas GN, Tomlison B, Chan JC, Young RP, Critchley JA (2000). The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome. Int J Obes Relat Metab Disord 24, 545–551.

    Article  CAS  Google Scholar 

  • Ueda K, Tanizawa Y, Oota Y, Inoue H, Kizuki N, Inoue H et al. (1997). Prevalence of the Trp64Arg missense mutation of the β3-adrenergic receptor gene in japanese subjects. Metabolism 46, 199–202.

    Article  CAS  Google Scholar 

  • Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Perusse L, Chagnon YC et al. (2000). Interaction among the α2-, β2- and β3-adrenergic receptor genes and obesity-related phenotypes in the Quebec family study. Metabolism 49, 1063–1070.

    Article  CAS  Google Scholar 

  • Urhammer SA, Clausen JO, Hansen T, Pedersen O (1996). Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the β3-adrenergic receptor gene. Diabetes 45, 1115–1120.

    Article  CAS  Google Scholar 

  • Walston J, Silver K, Hilfiker H, Andersen RE, Seibert M, Beamer B et al. (2000). Insulin response to glucose is lower in individuals homozygous for the Arg64 variant of the beta-3-adrenergic receptor. J Clin Endocrinol Metab 85, 4019–4022.

    CAS  PubMed  Google Scholar 

  • Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S et al. (1995). Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor-gene. N Engl J Med 333, 343–347.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Yoshida T, Sakane N, Umekawa T, Sakai M, Takahashi T, Kondo M (1995). Mutation of β3-adrenergic receptor of obesity. Lancet 246, 1433–1434.

    Article  Google Scholar 

  • Zaagsma J, Nahorski SR (1990). Is the adipocyte β-adrenoceptor a prototype for the recently cloned atypical β3-adrenoceptor? Trends Pharmacol Sci 11, 3–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Ministero delĺIstruzione, delĺUniversità e della Ricerca; COFIN 2004.

Author information

Authors and Affiliations

  1. Dipartimento S.P.E.S., Università del Molise, Campobasso, Italy

    R Bracale, G Salvatori & G Oriani

  2. CEINGE Biotecnologie Avanzate S.C. a r.l., Naples, Italy

    R Bracale, G Labruna, C Nardelli & L Sacchetti

  3. CISRO-Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy

    F Pasanisi, C Finelli & F Contaldo

  4. Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy

    G Labruna, C Nardelli & L Sacchetti

  5. Facoltà di Scienze Motorie, Università degli Studi Parthenope di Napoli, Naples, Italy

    P Buono

Authors
  1. R Bracale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Pasanisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Labruna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Finelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Nardelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Buono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Salvatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L Sacchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F Contaldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Oriani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F Pasanisi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bracale, R., Pasanisi, F., Labruna, G. et al. Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy. Eur J Clin Nutr 61, 1213–1219 (2007). https://doi.org/10.1038/sj.ejcn.1602640

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602640

Keywords

This article is cited by

Search

Advanced search

Quick links