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영남의대학술지 Vol.24 No.2 p252-261, Dec. 2007

Original Article

한국인에서 β3AR, UCP2 유전자의 다형성과 체질량지수의 관련성

Association Analyses of β3AR Trp64Arg and UCP-2 -866G/A Polymorphisms with Body Mass Index in Korean

정홍수, 이주현, 사공준*?배성욱†?김정희?김재룡
영남대학교 의과대학 생화학?분자생물학교실*, 예방의학교실†, 영남대학병원 건강증진센터†
책임저자:김재룡, 대구시 남구 대명5동 317-1, 영남대학교 의과대학 생화학?분자생물학교실
Tel: (053) 620-4342, Fax: (053) 654-6651
Email: kimjr@med.yu.ac.kr

December 30, 2007

Abstract

Background:Obesity is the most common nutritional disorder in Western society as well as in Korea. Obesity results from a combination of genetic, environmental, and behavioral factors.
Materials and Methods:In an attempt to investigate the association of obesity with its candidate genes, β3 adrenergic receptor (β3AR) and uncoupling protein 2 (UCP2), we analyzed polymorphisms of β3AR Trp64Arg and UCP2 -866G/A by PCR-RFLP analysis and the obesity-related phenotypes, including body mass index (BMI), fasting glucose concentration, and plasma lipid profiles in 750 subjects.
Results:The Trp64Arg polymorphism in the β3AR gene was not statistically associated with the BMI. The UCP2 -866G/A polymorphism was significantly higher in obese than in non-obese subjects (P<0.05). However, the UCP2 -866A/A polymorphism was higher in the non-obese subjects.
Conclusion:These results suggest that the UCP2 -866G/A polymorphism might be more useful for the prediction of obesity and obesity-associated diseases in Korean patients than the β3AR Trp64Arg polymorphism.

본 연구는 영남대학교 선도연구비(105098)의 지원을 받아 이루어졌다.

Key Words: Obesity, Beta-3 adrenergic receptor, Uncoupling protein 2, Polymorphism, Body Mass Index

References

1. Friedman JM. Obesity in the new millennium. Nature 2000 Apr;404:632-4.

2. Bray GA, Tartaglia LA. Medicianl strategies in the treatment of obesity. Nature 2000 Apr; 404:672-7.

3. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1995 Mar;372:425-32.

4. Rosmond R. Association studies of genetic polymorphisms in central obesity: a critical review. Int J Obes Relat Metab Disord 2003 Oct;27:1141-51.

5. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998 Mar;18:213-5.

6. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000 Apr;404:661-71.

7. Hinney A, Becker I, Heibult O, Nottebom K, Schmidt A, Ziegler A, et al. Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes. J Clin Endocrinol Metab 1998 Oct;83:3737-41.

8. Wilson BD, Ollmann MM, Barsh GS. The role of agouti-related protein in regulating body weight. Mol Med Today 1999 Jun;5:250-6.

9. Rosmond R, Chagnon M, Bouchard C, Bjorntorp P. A missense mutation in the human melanocortin-4 receptor gene in relation to abdominal obesity and salivary cortisol. Diabetologia 2001 Oct;44:1335-8.

10. Esterbauer H, Schneitler C, Oberkofler H, Ebenbichler C, Paulweber B, Sandhofer F, et al. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet 2001 Jun;28:178-83.

11. Lowell BB, Flier JS. Brown adipose tissue, β3-adrenergic receptors, and obesity. Annu Rev Med 1997 Feb;48:307-16.

12. Clement K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, et al. Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995 Aug;333:352-4.

13. Oizumi T, Daimon M, Saitoh T, Kameda W, Yamaguchi H, Ohnuma H, et al. Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the β3-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample. Diabetes Care 2001 Sep;24:1579-83.

14. Swarbrick MM, Chapman CM, McQuillan BM, Hung J, Thompson PL, Beilby JP. A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity. Eur J Endocrinol 2001 Mar;144:277-82.

15. 김병준, 김성훈, 김동준, 함종렬, 김진석, 안규정, 등. 한국인 비만증에서 β3 아드레날린 수용체 유전자 다형성의 의의. 당뇨병 1998 Oct;50:450-6.

16. 박석원, 이현철, 권석주, 조은영, 이종호, 송영득, 등. 비만인에서 베타3-아드레날린성 수용체 유전자변이에 따른 체지방 분포양상과 체중감량의 효과. 대한내분비학회지 1998 Oct;13:590-600.

17. 윤태승, 김용득, 김혜순, 김미정, 서영성, 권중혁, 등. 베타3-아드레날린성 수용체 유전자 변이와 체지방 분포. 대한내분비학회지 2003 Jan;18: 184-92.

18. Park HS, Kim Y, Lee C. Single nucleotide variants in the β2-adrenergic and β3-adrenergic receptor genes explained 18.3% of adolescent obesity variation. J Hum Genet 2005 Jun;50: 365-9.

19. 김혜순, 이인규, 서영성. 멜라노코틴-4 수용체 유전자 다형성과 비만과의 관계. 당뇨병 2003 Mar;27:123-31.

20. Salisbury BA, Pungliya M, Choi JY, Jiang R, Sun XJ, Stephens JC. SNP and haplotype variation in the human genome. Mutat Res 2003 May;526:53-61.

21. van Baak MA. The peripheral sympathetic nervous system in human obesity. Obes Rev 2001 Feb;2:3-14.

22. Collins S, Daniel KW, Rohlfs EM, Ramkumar V, Taylor IL, Gettys TW. Impaired expression and functional activity of the β3- and β1- adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. Mol Endocrinol 1994 Apr;8:518-27.

23. Grujic D, Susulic VS, Harper ME, Himms- Hagen J, Cunningham BA, Corkey BE, et al. β3-adrenergic receptors on white and brown adipocytes mediate β3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake. A study using transgenic and gene knockout mice. J Biol Chem 1997 Jul;272:17686-93.

24. Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, et al. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene. N Engl J Med 1995 Aug;333:343-7.

25. 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. N Engl J Med 1995 Aug;333:348-51.

26. Ghosh S, Langefeld CD, Ally D, Watanabe RM, Hauser ER, Magnuson VL, et al. The W64R variant of the β3-adrenergic receptor is not associated with type II diabetes or obesity in a large Finnish sample. Diabetologia 1999 Feb;42:238-44.

27. Janssen JA, Koper JW, Stolk RP, Englaro P, Uitterlinden AG, Huang Q, et al. Lack of associations between serum leptin, a polymorphism in the gene for the β3-adrenergic receptor and glucose tolerance in the Dutch population. Clin Endocrinol (Oxf) 1998 Aug;49: 229-34.

28. Jezek P. Possible physiological roles of mitochondrial uncoupling proteins-UCPn. Int J Biochem Cell Biol 2002 Oct;34:1190-206.

29. Le Fur S, Le Stun. C, Dos Santos C, Bougneres P. The common -866G/A polymorphism in the promoter of uncoupling protein 2 is associated with increased carbohydrate and decreased lipid oxidation in juvenile obesity. Diabetes 2004 Jan;53:235-9.

30. Schauble N, Geller F, Siegfried W, Goldschmidt H, Remschmidt H, Hinney A, et al. No evidence for involvement of the promoter polymorphism -866G/A of the UCP2 gene in childhood-onset obesity in humans. Exp Clin Endocrinol Diabetes 2003 Apr;111:73-6.