Full Text:
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.