Download PDF
Exp Clin Endocrinol Diabetes 2005; 113(10): 593-597
DOI: 10.1055/s-2005-872840
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The Trp64Arg β3-Adrenergic Receptor Amino-Acid Variant is not Associated with Overweight and Type 2 Diabetes Mellitus in Polish Population

J. Kasznicki1 , J. Blasiak2 , I. Majsterek2 , K. Przybyłowska2 , J. Drzewoski1
  • 1Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
  • 2Department of Molecular Genetics, University of Lodz, Lodz, Poland
Further Information

Publication History

Received: November 19, 2004 First decision: January 5, 2005

Accepted: August 22, 2005

Publication Date:
30 November 2005 (online)

Also available at
    Permissions and Reprints

Abstract

The Trp64Arg amino-acid variant of the β3 adrenoreceptor gene may be associated with a genetic predisposition to human obesity and related disorders, including type 2 diabetes mellitus. This relationship has been reported in various ethnic groups, however it was not extensively studied in Polish population. Therefore, the aim of the study was to investigate the association of Trp64Arg polymorphism of the β3 adrenergic receptor gene with overweight and type 2 diabetes mellitus in polish subjects. The Trp64Arg polymorphism was determined by PCR-based MspI restriction fragment length polymorphism (PCR-RFLP). The study population consisted of 358 subjects, among whom 200 were diagnosed as overweight (BMI > 27 kg/m2). Among overweight subjects 111 presented with type 2 diabetes mellitus and 89 with normal glucose metabolism. All study participants were unrelated Caucasians and inhabited the city of Lodz, Poland. The frequency of the Arg allele did not differ significantly between overweight and normal weight patients (13 % vs. 11 %, OR 1.17, CI 0.74 - 1.85). The same applied to overweight diabetic patients vs. overweight patients without diabetes mellitus (13 % vs. 13 %, OR 0.97, CI 0.54 - 1.76). The obtained results suggest no association between Trp64Arg polymorphism of the β3-AR gene and the incidence of overweight and type 2 diabetes mellitus in Polish population.

Key words

β3-adrenergic receptor - genetic polymorphism - overweight - type 2 diabetes mellitus

References

  • 1 Allison D B, Heo M, Faith M S, Pietrobelli A. Meta-analysis of the association of the Trp64Arg polymorphism in the β3 adrenergic receptor with body mass index.  Int J Obes Relat Metab Disord. 1998;  22 559-566
    CrossrefPubMedGoogle Scholar
  • 2 Arch J R, Kaufmann A J. Beta 3 and atypical beta-adrenoreceptors.  Med Res Rev. 1993;  13 663-729
    PubMedGoogle Scholar
  • 3 Arner P. The β3-adrenergic receptor - a cause and cure of obesity?.  N Engl J Med. 1995;  333 382-383
    CrossrefPubMedGoogle Scholar
  • 4 Birnbaumer M. Mutations and diseases of G protein coupled receptors.  J Recept Signal Transduct Res. 1995;  15 131-160
    PubMedGoogle Scholar
  • 5 Clement K, Vaisse C, Manning B S, Basdevant A, Guy-Grand B, Ruiz J, Silver K D, Shuldiner A R, Froguel P, Strosberg A D. Genetic variations in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity.  N Engl J Med. 1995;  333 352-354
    CrossrefPubMedGoogle Scholar
  • 6 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Report of the expert committee on the diagnosis and classification of diabetes mellitus [from the American Diabetes Association, ADA].  Diabetes Care. 2002;  25 (Suppl 1) S1-S20
    PubMedGoogle Scholar
  • 7 Fujisawa T, Ikegami H, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Oga T, Ueda H, Shintani M, Fukuda M, Ogihara T. Association of Trp64Arg mutation of the beta3-adrenergic receptor with NIDDM and body weight gain.  Diabetologia. 1996;  39 349-352
    PubMedGoogle Scholar
  • 8 Gagnon J, Mauriege P, Roy S, Sjostrom D, Chagnon Y C, Dionne F T, Oppert J M, Perusse L, Sjostrom L, Bouchard C. The Trp64Arg mutation of the beta 3 adrenergic receptor gene has no effect on obesity phenotypes in the Quebec Family Study and Swedish Obese Subjects cohorts.  J Clin Invest. 1996;  98 2086-2093
    PubMedGoogle Scholar
  • 9 Kurabayashi T, Carey D G, Morrison N A. The beta3-adrenergic receptor gene Trp64Arg mutation is overrepresented in obese women. Effects on weight, BMI, abdominal fat, blood pressure, and reproductive history in an elderly Australian population.  Diabetes. 1996;  45 1358-1363
    PubMedGoogle Scholar
  • 10 Li L S, Lonnqvist F, Luthman H, Arner P. Phenotypic characterization of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene in normal weight and obese subjects.  Diabetologia. 1996;  39 857-860
    CrossrefPubMedGoogle Scholar
  • 11 Lonnqvist F, Home A, Nilsell K, Hoffstedt J, Arner P. A pathogenic role of visceral fat beta 3-adrenoceptors in obesity.  J Clin Invest. 1995;  95 1109-1116
    PubMedGoogle Scholar
  • 12 Manraj M, Francke S, Hebe A, Ramjuttun U S, Froguel P. Genetic and environmental nature of the insulin resistance syndrome in Indo-Mauritian subjects with premature coronary heart disease: contribution of β3-adrenoreceptor gene polymorphism and beta blockers on triglyceride and HDL concentrations.  Diabetologia. 2001;  44 115-122
    CrossrefPubMedGoogle Scholar
  • 13 Marti A, Corbalan M S, Martinez-Gonzalez M A, Martinez J A. Trp64Arg polymorphism of the β3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle.  Diabetes Obes Metab. 2002;  4 428-430
    CrossrefPubMedGoogle Scholar
  • 14 Melis M G, Secchi G, Brizzi P, Severino C, Maioli M, Tonolo G. The Trp64 Arg β3-adrenergic receptor amino acid variant confers increased sensitivity to the pressor effects of noradrenaline in Sardinian subjects.  Clinical Science. 2002;  103 397-402
    PubMedGoogle Scholar
  • 15 Mizuno K, Kanda Y, Kuroki Y, Watanabe Y. The stimulation of β3-adrenoceptor causes phosphorylation of extracellular signal-regulated kinases 1 and 2 through a Gs- but not Gi-dependent pathway in 3T3-L1 adipocytes.  Eur J Pharmacol. 2000;  404 63-68
    CrossrefPubMedGoogle Scholar
  • 16 Moriarty M, Wing R R, Kuller L H, Ferrell R E. Trp64Arg substitution in the β3-adrenergic receptor does not relate to body weight in healthy, premenopausal women.  Int J Obesity. 1996;  21 826-829
    PubMedGoogle Scholar
  • 17 Muzzin P, Revelli J P, Kuhne F, Gocayne J D, McCombie W R, Venter J C, Giacobino J P, Fraser C M. An adipose tissue-specific beta-adrenergic receptor. Molecular cloning and down-regulation in obesity.  J Biol Chem. 1991;  256 24053-24058
    PubMedGoogle Scholar
  • 18 Rawson E S, Nolan A, Silver K, Shuldiner A R, Poehlman E T. No effect of the Trp64Arg beta(3)-adrenoceptor gene variant on weight loss, body composition, or energy expenditure in obese, caucasian postmenopausal women.  Metabolism. 2002;  51 801-805
    CrossrefPubMedGoogle Scholar
  • 19 Strazzullo P, Iacone R, Siani A, Cappucino F P, Russo O, Barba G, Barbato A, D'Elia L, Trevisian M, Farinaro E. Relationship of the 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. 2001;  19 399-406
    CrossrefPubMedGoogle Scholar
  • 20 Tataranni P A, Pratley R, Shuldiner A, Ravussin E. Beta3-adrenergic receptor gene variant and lipid metabolism in Pima Indians.  Diabetologia. 1997;  40 123-124
    CrossrefPubMedGoogle Scholar
  • 21 Tonolo G, Melis M G, Secchi G, Atzeni M M, Angius M F, Carboni A, Ciccarese M, Malavasi A, Maioli M. Association of Trp64Arg beta3-adrenergic-receptor gene polymorphism with essential hypertension in the Sardinian population.  J Hypertens. 1999;  17 33-38
    PubMedGoogle Scholar
  • 22 Umekawa T, Yoshida T, Sakane N, Kogure A, Kondo M, Honjyo H. Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lypolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.  Diabetes. 1999;  48 117-120
    PubMedGoogle Scholar
  • 23 Walston J, Silver K, Bogardus C, Knowler W C, Celi F S, Austin S, Manning B, Strosberg A D, Stern M P, Raben N. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene.  N Engl J Med. 1995;  333 343-347
    CrossrefPubMedGoogle Scholar
  • 24 Widen E, Lehto M, Kanninen T, Walston J, Shuldiner A R, Groop L C. Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns.  N Engl J Med. 1995;  333 348-351
    CrossrefPubMedGoogle Scholar
  • 25 Yen T T. Beta-agonists as antiobesity, antidiabetic and nutritient partitioning agents.  Obes Res. 1995;  3 531S-536S
    PubMedGoogle Scholar

MD, PhD Jacek Kasznicki

Department of Clinical Pharmacology
Medical University of Lodz

Lodz

Poland

Email: jkasznicki@up.pl