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Effect of a three-amino acid deletion in the α2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects

Abstract

BACKGROUND AND OBJECTIVE: The short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the α2B-adrenergic receptor gene was previously found to be associated with reduced basal metabolic rate in obese subjects. We investigated the effects of this polymorphism on changes in body weight in Finnish non-diabetic and type 2 diabetic subjects during a 10 y follow-up.

DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations.

SUBJECTS: A total of 126 non-diabetic control subjects and 84 newly diagnosed, middle-aged type 2 diabetic patients from eastern Finland participated.

MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and glycosylated hemoglobin A1c. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis.

RESULTS: No significant differences were found in the prevalence of the 12Glu9 deletion polymorphism between non-diabetic and type 2 diabetic subjects. The non-diabetic subjects with the Glu9/Glu9 genotype had a greater increase in their mean body weight during 5 y follow-up than the non-diabetic subjects with other genotypes (changes in body weight 0.4±5.7, −0.5±6.4 and 3.4±4.9% for the Glu12/Glu12, Glu12/Glu9 and Glu9/Glu9 genotypes, respectively, P=0.040 for the difference between the groups). Also, the trend for the increment of body weight was statistically significant in the non-diabetic subjects with the Glu9/Glu9 genotype (P=0.012). The 12Glu9 polymorphism was not cross-sectionally or longitudinally associated with body weight in type 2 diabetic subjects.

CONCLUSIONS: The genotype of two short alleles (Glu9/Glu9) was associated with an increase in body weight among non-diabetic subjects.

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References

  1. Chagnon YC, Perusse L, Weisnagel SJ, Rankinen T, Bouchard C . The human obesity gene map: the 1999 update Obesity Res 2000 8: 89–117.

    Article  CAS  Google Scholar 

  2. Coughlin SR . Expanding horizons for receptors coupled to G proteins. Diversity and disease Curr Opin Cell Biol 1994 6: 191–197.

    Article  CAS  Google Scholar 

  3. Spraul M, Ravussin E, Fontvieille AM, Rising R, Larsson DE, Andersson EA . Reduced sympathetic nervous activity: a potential mechanism predisposing to body weight gain J Clin Invest 1993 92: 1730–1735.

    Article  CAS  PubMed Central  Google Scholar 

  4. Large V, Hellström L, Reynisdottir S, Lönnqvist F, Eriksson P, Lannfelt L, Arner P . Human β2-adrenoceptor polymorphisms are highly frequent in obesity and associate with altered adipocyte β2-adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  PubMed Central  Google Scholar 

  5. Sipiläinen R, Uusitupa M, Heikkinen S, Rissanen A, Laakso M . Polymorphism of the β3-adrenergic receptor gene affects basal metabolic rate in obese Finns Diabetes 1997 46: 77–80.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Nicholas AP, Hökfelt T, Pieribone VA . The distribution and significance of CNS adrenoceptors examined with in situ hybridization Trends Pharmac Sci 1996 17: 245–255.

    Article  CAS  Google Scholar 

  8. Bylund DB . Subtypes of alpha 1- and alpha 2-adrenergic receptors FASEB J 1992 6: 832–839.

    Article  CAS  Google Scholar 

  9. Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka TS, Francke U, Lefkowitz RJ, Caron MG . An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins Nature 1987 329: 75–79.

    Article  CAS  Google Scholar 

  10. Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK . Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype Proc Natl Acad Sci USA 1988 85: 6301–6305.

    Article  CAS  Google Scholar 

  11. Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL, Caron MG, Lefkowitz RJ . Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2 Proc Natl Acad Sci USA 1990 87: 5094–5098.

    Article  CAS  Google Scholar 

  12. MacMillan LB, Hein L, Smith MS, Piascik MT, Limbird LE . Central hypotensive effects of the alpha2a-adrenergic receptor subtype Science 1996 273: 801–803.

    Article  CAS  Google Scholar 

  13. Link RE, Desai K, Hein L, Stevens ME, Chruscinski A, Bernstein D, Barsh GS, Kobilka BK . Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c Science 1996 273: 803–805.

    Article  CAS  Google Scholar 

  14. Ruffolo RR Jr, Nichols AJ, Stadel JM, Hieble JP . Pharmacologic and therapeutic applications of α2-adrenoceptor subtypes A Rev Pharmac Toxicol 1993 32: 243–279.

    Article  Google Scholar 

  15. Lockette W, Ghosh S, Farrow S, MacKenzie S, Miles P, Schork A, Cadaret L . α2-adrenergic receptor gene polymorphism and hypertension in blacks Am J Hypertens 1995 8: 390–394.

    Article  CAS  Google Scholar 

  16. Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M, Valve R, Uusitupa M, Scheinin M . Identification of a three-amino acid deletion in the α2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects J Clin Endocrinol Metab 1999 84: 2429–2433.

    CAS  PubMed  Google Scholar 

  17. Uusitupa M, Siitonen O, Aro A, Pyörälä K . Prevalence of coronary heart disease, left ventricular failure and hypertension in middle-aged, newly diagnosed type 2 (noninsulin-dependent) diabetic subjects Diabetologia 1988 28: 22–27.

    Article  Google Scholar 

  18. Niskanen L, Karjalainen J, Siitonen O, Uusitupa M . Metabolic evolution of type 2 diabetes: 10-year follow-up J Intern Med 1994 236: 263–270.

    Article  CAS  Google Scholar 

  19. World Health Organization . WHO Expert Committee on Diabetes Mellitus, Second Report Technical Report Series no. 646 WHO: Geneva 1980

    Google Scholar 

  20. Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, Boyce V, Howard BV, Bogardus C . Reduced rate of energy expenditure as a risk factor for body-weight gain New Engl J Med 1988 318: 467–472.

    Article  CAS  Google Scholar 

  21. Jewell-Motz EA, Liggett SB . An acidic motif within the third intracellular loop of the α2C2 adrenergic receptor is required for agonist-promoted phosphorylation and desensitization Biochemistry 1995 34: 11946–11953.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Finnish Foundation of Diabetes Research and the Academy of Finland.

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Correspondence to K Sivenius.

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Sivenius, K., Lindi, V., Niskanen, L. et al. Effect of a three-amino acid deletion in the α2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects. Int J Obes 25, 1609–1614 (2001). https://doi.org/10.1038/sj.ijo.0801798

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