Abstract
Associations of obesity with its candidate genes, β-adrenergic receptor genes (ADRBs), peroxisome proliferator-activated receptor-γ (PPARγ), and uncoupling proteins (UCPs) were studied in Korean adolescents. We analyzed the obesity-related phenotypes body mass index (BMI), percentage of body fat, plasma leptin and insulin levels, fasting glucose concentration, and plasma lipid profile in 329 teenagers to investigate the effects of seven single nucleotide variants 252G/A, 523C/A and 1053G/C in ADRB2; Trp64Arg in ADRB3; 161C/T in PPARγ; Ala55Val in UCP2; and 210C/T in UCP3. The 1053G/C polymorphism (P < 0.05) in the ADRB2 gene and the Trp64Arg polymorphism (P < 0.01) in the ADRB3 gene were associated with BMI after adjustment for dietary energy intake. Trp64Arg polymorphism also influenced percentage of body fat (P < 0.01) and plasma leptin level (P < 0.05). Furthermore, significant interaction effects between the 1053G/C and Trp64Arg polymorphisms were observed on BMI (P < 0.01). The polymorphisms of the ADRB2 and ADRB3 genes explained 4.3% and 10.1% of the variation on BMI, and the two loci effect, including their epistasis, explained 18.3%. We concluded that 1053G/C and Trp64Arg polymorphisms of the ADRB genes additively and interactively contributed to the variation of complex adolescent obesity.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Arashiro R, Katsuren K, Fukuyama S, Ohta T (2003) Effect of Trp64Arg mutation of the β3-adrenergic receptor gene and C161T substitution of the peroxisome proliferator activated receptor gamma gene on obesity in Japanese children. Pediatr Int 45:135–141
Chagnon YC, Perusse L, Weisnagel SJ, Rankinen T, Bouchard C (2000) The human obesity gene map: the 1999 update. Obes Res 8:89–117
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1240–1243
Corella D, Guillen M, Portoles O, Sorli JV, Alonso V, Folch J, Saiz C (2001) Gender-specific associations of the Trp64Arg mutation in the β3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. J Intern Med 250:348–360
Dalgaard LT, Pedersen O (2001) Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes. Diabetologia 44:946–965
Damcott CM, Feingold E, Moffett SP, Barmada MM, Marshall JA, Hamman RF, Ferrell RE (2002) Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study. J Appl Physiol 92:1111–1118
Endo K, Yanagi H, Hirano C, Hamaguchi H, Tsuchiya S, Tomura S (2000) Association of Trp64Arg polymorphism of the β3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity. Int J Obes Relat Metab Disord 24:443–449
Hao K, Peng S, Xing H, Yu Y, Huang A, Hong X, Wang Y, Chen C, Wang B, Zhang X, Liu J, Zhu G, Huo Y, Chen D, Zhao X, Ronnenberg A, Wu D, Niu T, Xu X (2004) β3 Adrenergic receptor polymorphism and obesity-related phenotypes in hypertensive patients. Obes Res 12:125–130
Jaberi E (2004) Genetic linkage of uncoupling proteins (UCP2 and UCP3) with body weight regulation. Asia Pac J Clin Nutr 13 (Suppl):S140
Lanouette CM, Chagnon YC, Rice T, Perusse L, Muzzin P, Giacobino JP, Gagnon J, Wilmore JH, Leon AS, Skinner JS, Rao DC, Bouchard C (2001) Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study. Mol Med 7:433–441
Le Fur S, Le Stunff C, Dos Santos C, Bougneres P (2004) The common −866 G/A polymorphism in the promoter of uncoupling protein 2 is associated with increased carbohydrate and decreased lipid oxidation in juvenile obesity. Diabetes 53:235–239
Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–660
Maestrini S, Podesta F, Di Blasio AM, Savia G, Brunani A, Tagliaferri A, Mencarelli M, Chiodini I, Liuzzi A (2003) Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians. J Endocrinol Invest 26:985–990
Peng DQ, Zhao SP, Nie S, Li J (2003) Gene-gene interaction of PPARγ and ApoE affects coronary heart disease risk. Int J Cardiol 92:257–263
Schauble N, Geller F, Siegfried W, Goldschmidt H, Remschmidt H, Hinney A, Hebebrand J (2003) No evidence for involvement of the promoter polymorphism −866 G/A of the UCP2 gene in childhood-onset obesity in humans. Exp Clin Endocrinol Diabetes 111:73–76
Sorensen TI, Sonne-Holm S (1988) Risk in childhood of development of severe adult obesity: retrospective, population-based case-cohort study. Am J Epidemiol 127:104–113
Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Perusse L, Chagnon YC, Despres JP, Bouchard C (2000) Interactions among the α2-, β2-, and β3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study. Metabolism 49:1063–1070
Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, Manning B, Strosberg AD, Raben N, Sorkin JD, Stern MP, Roth J, Shuldiner AR (1995) Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. N Engl J Med 333:343–347
Wang XL, Oosterhof J, Duarte N (1999) Peroxisome proliferator-activated receptor γ C161→T polymorphism and coronary artery disease. Cardiovasc Res 44:588–594
Wang H, Chu WS, Lu T, Hasstedt SJ, Kern PA, Elbein SC (2004) Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion. Am J Physiol Endocrinol Metab 286:E1–E7
Yanovski JA, Diament AL, Sovik KN, Nguyen TT, Li H, Sebring NG, Warden CH (2000) Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children. Am J Clin Nutr 71:1405–1420
Acknowledgements
We would like to thank the volunteers and their parents who participated in this study. This study was supported by a grant from the Korea Science & Engineering Foundation, Korea (R04-2001-00020) and by a grant from Hallym University, Korea.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, H.S., 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 50, 365–369 (2005). https://doi.org/10.1007/s10038-005-0260-x
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1007/s10038-005-0260-x
