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:

The Trp64Arg polymorphism of the β3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome

International Journal of Obesity volume 24, pages 545–551 (2000)Cite this article

Abstract

BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome.

OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the β3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders.

METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia.

RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the χ2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI.

CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.

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. Reaven GM . Banting Lecture 1988: role of insulin resistance in human disease Diabetes 1988 37: 1595–1607.

    Article  CAS  Google Scholar 

  2. Chan JCN, Cheung JCK, Lau EMC, Woo J, Chan AYW, Cockram CS . The metabolic syndrome in Hong Kong Chinese. The interrelationships among its components analyzed by structural equation modeling Diabetes Care 1996 19: 953–959.

    Article  CAS  Google Scholar 

  3. Després JP, Allard C, Tremblay A, Talbot J, Bouchard C . Evidence for a regional component of body fatness in the association with serum lipids in men and women Metabolism 1985 34: 967–973.

    Article  Google Scholar 

  4. Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Tokunaga K . Pathophysiology and pathogenesis of visceral fat obesity Ann NY Acad Sci 1983 676: 270–278.

    Article  Google Scholar 

  5. Keesey RE . Physiological regulation of body energy. Implications for obesity. In: Stunkard AJ, Wadden TA (eds) Obesity: theory and therapy. Raven Press: New York 1993 pp 77–96.

    Google Scholar 

  6. Strosberg AD, Pietri-Rouxel F . Function and regulation of the β3-adrenoceptor Trends Pharmacol Sci 1996 17: 373–381.

    Article  CAS  Google Scholar 

  7. Zilberfarb V, Pietri-Rouxel F, Jockers R, Krief S, Delouis C, Issad T, Strosberg AD . Human immortalized brown adipocytes express functional beta3-adreceptor coupled to lipolysis J Cell Sci 1997 110: 801–807.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Kadowaki H, Yasuda K, Iwamoto K, Otabe S, Shimokawa K, Silver K, Walston J, Yoshinaga H, Kosaka K, 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 hyperinsulinaemia in Japanese subjects Biochem Biophys Res Commun 1995 215: 555–560.

    Article  CAS  Google Scholar 

  10. Knowler WC . Association of Trp64Arg mutation of the β3-adrenergic receptor gene with NIDDM Diabetologia 1996 39: 1411.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. 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 β3-adrenergic receptor with NIDDM and body weight gain Diabetologia 1996 39: 349–352.

    Article  CAS  Google Scholar 

  13. Clement K, Vaisse C, Manning SJB, 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 N Engl J Med 1995 333: 352–354.

    Article  CAS  Google Scholar 

  14. McFarlane-Anderson N, Bennett F, Wilks R, Howell S, Newsome C, Cruickshank K, Forrester T . The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women Metabolism 1998 47: 617–621.

    Article  CAS  Google Scholar 

  15. Kim-Motoyama H, Yasuda K, Yamguichi T, Yamada N, Katkura T, Shuldiner AR, Akanuma Y, Ohashi Y, Yazaki Y, Kadowaki T . A mutation of the beta 3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride Diabetologia 1997 40: 469–472.

    Article  CAS  Google Scholar 

  16. Strosberg AD . Association of β3-adrenoceptor polymorphism with obesity and diabetes: current status Trends Pharmac Sci 1997 18: 449–454.

    Article  CAS  Google Scholar 

  17. Odawara M, Sasaki K, Yamashita K . β3-adrenergic receptor gene variant and Japanese NIDDM: a pitfall in meta-analysis Lancet 1996 348: 896–897.

    Article  CAS  Google Scholar 

  18. Rissanen J, Kuopusjarvi M, Pihlajamaki J, Sipilainen R, Heikkinen S, Vanhala M, Kekalainen P, Kuusisto J, Laasko M . The Trp64Arg polymorphism of the β3-adrenergic receptor gene. Lack of association with NIDDM and features of insulin resistance syndrome Diabetes Care 1997 20: 1319–1323.

    Article  CAS  Google Scholar 

  19. Mauriege P, Bouchard C . Trp64Arg mutation in beta 3-adrenoceptor gene of doubtful significance for obesity and insulin resistance Lancet 1996 348: 698–699.

    Article  CAS  Google Scholar 

  20. Shuldiner AR, Silver K, Roth J, Walston J . Beta 3-adrenoceptor gene variant in obesity and insulin resistance Lancet 1996 348: 1584–1585.

    Article  CAS  Google Scholar 

  21. Strosberg AD, Froguel F . Beta 3-adrenoceptor gene variant in obesity and insulin resistance Lancet 1996 348: 1585.

    Article  CAS  Google Scholar 

  22. Chan JCN, Cockram CS . Diabetes in the Chinese population and its implications for health care Diabetes Care 1997 20: 1785–1790.

    Article  CAS  Google Scholar 

  23. The Expert Committee on the Diagnosis and Classification of Diabetes mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes mellitus Diabetes Care 1997 20: 1183–1197.

  24. JNC-VI . The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure Ann Intern Med 1997 157: 2413–2446.

    Article  Google Scholar 

  25. Guide to plasma lipids and lipoproteins for Hong Kong doctors J Hong Kong Coll Cardiol 1996 4: 81–89.

  26. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation and treatment of high blood cholesterol in adults JAMA 1993 269: 3015–3023.

  27. Xiang K, Jia W, Lu H, Zheng T, Lu J, Tang J, Ding W, Sun D, Li J . Effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on body fat, plasma glucose level, lipid profile, insulin secretion and action (in Chinese) Chung Hua I Hsueh I Chuan Hseuh Tsa Chih 1998 15: 337–340.

    CAS  Google Scholar 

  28. Silver K, Walston J, Wang Y, Dowse G, Zimmet P, Shuldiner AR . Molecular screening for mutations in the adrenergic β3-adrenergic receptor gene in Nauruans with obesity and noninsulin diabetes mellitus J Clin Endocrinol Metab 1996 81: 4155–4158.

    CAS  Google Scholar 

  29. Martin BC, Warram JH, Rosner B, Rich SS, Soeldner JS, Krowlewski AS . Familial clustering of insulin sensitivity Diabetes 1992 41: 850–854.

    Article  CAS  Google Scholar 

  30. Mitchell BD, Kammerer CM, Mahaney MC, Blangero J, Comuzzie AG, Atwood LD, Haffner SM, Stern MP, MacCluer JW . Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures Arterioscler Thromb Vasc Biol 1996 16: 281–288.

    Article  CAS  Google Scholar 

  31. Kurabayashi T, Carey DGP, Morrison NA . The β3-adrenergic receptor gene Trp64Arg mutation is over represented in obese women Diabetes 1996 45: 1358–1363.

    Article  CAS  Google Scholar 

  32. Urhammer SA, Clausen JO, Hansen T, Pedersen O . Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the β3-adrenergic receptor gene Diabetes 1996 45: 115–1120.

    Article  Google Scholar 

  33. Ueda K, Tanizawa Y, Oota Y, Inoue H, Kizuki N, Tsukuda K, Asano T, Oka Y . Prevalence of the Trp64Arg missense mutation of the beta3-adrenergic receptor gene in Japanese subjects Metabolism 1997 46: 199–202.

    Article  CAS  Google Scholar 

  34. Awata T, Katayama S . Genetic variation in the β3-adrenergic receptor in Japanese NIDDM patients Diabetes Care 1996 19: 271–272.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Hong Kong Research Grants Council grants CUHK 237/94M, CUHK 426/95M and Strategic Research Programme grants 9702 and 9902 as well as Project grant 2040721.

Author information

Author notes

  1. RP Young

    Present address: Department of Medicine, University of Auckland, Auckland Hospital, Park Rd, Auckland, New Zealand

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China

    GN Thomas, B Tomlinson, JCN Chan, RP Young & JAJH Critchley

Authors
  1. GN Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. JCN Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. RP Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. JAJH Critchley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to GN Thomas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thomas, G., Tomlinson, B., Chan, J. et al. The Trp64Arg polymorphism of the β3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome. Int J Obes 24, 545–551 (2000). https://doi.org/10.1038/sj.ijo.0801193

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801193

Keywords

This article is cited by

Search

Advanced search

Quick links