Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

International Review of Psychiatry

Volumn 24, Issue 3, 2012, Pages 200-210

  Cecil, Joanne ^a   Dalton, Michelle ^b   Finlayson, Graham ^b   Blundell, John ^b   Hetherington, Marion ^b   Palmer, Colin ^c  

^a UNIVERSITY OF ST ANDREWS   (United Kingdom)

^b UNIVERSITY OF LEEDS   (United Kingdom)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BODY FAT; BODY MASS; DNA POLYMORPHISM; ENERGY BALANCE; FAT MASS AND OBESITY ASSOCIATED GENE; FEEDING BEHAVIOR; GENE; GENE MUTATION; GENETIC VARIABILITY; HERITABILITY; HUMAN; LEPTIN RECEPTOR GENE; MELANOCORTIN 4 RECEPTOR GENE; OBESITY; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GENE; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOLESCENT; APPETITE; CHILD; ENERGY METABOLISM; FEEDING BEHAVIOR; HUMANS; OBESITY; POLYMORPHISM, GENETIC; PPAR GAMMA; PROTEINS; RECEPTOR, MELANOCORTIN, TYPE 4;

EID: 84862842223     PISSN: 09540261     EISSN: 13691627     Source Type: Journal    
DOI: 10.3109/09540261.2012.685056     Document Type: Review

References (151)

1. Agurs-Collins, T. & Fuemmeler, B.F. (2011). Dopamine polymorphisms and depressive symptoms predict foods intake. Results from a nationally representative sample. Appetite, 57, 339-348.
2. Andreasen, C.H., Stender-Petersen, K.L., Mogensen, M.S., Torekov, S.S., Wegner, L., Andersen, G., Hansen, T. (2008). Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes, 57, 95-101.
3. Angeli, C.B., Kimura, L., Auricchio, M.T., Vicente, J.P., Mattevi, V.S., Zembrzuski, V.M., Mingroni-Netto, R.C. (2011). Multilocus analyses of seven candidate genes suggest interacting pathways for obesity-related traits in Brazilian Populations. Obesity, 19, 1244-1251.
4. Aoyama, M., Shidoji, Y., Saimei, M., Tsunawake, N. & Ichinose, M. (2003). Phenotypic linkage between single-nucleotide polymorphisms of beta3-adrenergic receptor gene and NADH dehydrogenase subunit-2 gene, with special reference to eating behavior. Biochem Biophys Res Commun, 309, 261-265.
5. Arashiro, R., Katsuren, K., Fukuyama, S. & Ohta, T. (2003). Effect of Trp64Arg mutation of the beta3-adrenergic receptor gene and C161T substitution of the peroxisome proliferator activated receptor gamma gene on obesity in Japanese children. Pediatrics International, 45, 135-141.
6. Auwerx, J. (1999). PPARgamma, the ultimate thrifty gene. Diabetologia, 42, 1033-1049.
7. Balthasar, N., Dalgaard, L.T., Lee, C.E., Yu, J., Funahashi, H., Williams, T., Lowell, B.B. (2005). Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell, 123, 493-505.
8. Beamer, B.A., Yen, C.J., Andersen, R.E., Muller, D., Elahi, D., Cheskin, L.J., Shuldiner, A.R. (1998). Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes, 47, 1806-1808.
9. Berthoud, H.R. (2004). Neural control of appetite: Cross-talk between homeostatic and non-homeostatic systems. Appetite, 43, 315-317.
10. Blum, K., Braverman, E.R., Wood, R.C., Gill, J., Li, C., Chen, T.J., Cull, J.G. (1996). Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: A preliminary report. Pharmacogenetics, 6, 297-305.
11. Blundell JE, de Graaf K, Finlayson G, Halford J, Hetherington MM, King N, Stubbs R. (2009). Measuring Food Intake, Hunger, Satiety and Satiation in the Laboratory. In Allison DB & Baskin ML (Ed.), Handbook of Assessment Methods for Eating Behaviors and weight related problems: Measures, Theory and Research . Newbury Park: Sage Publications.
12. Bouchard-Mercier, A., Godin, G., Lamarche, B., Perusse, L. & Vohl, M.-C. (2011). Effects of peroxisome proliferator-activated receptors, dietary fat intakes and gene-diet interactions on peak particle diameters of low-density lipoproteins. Journal of Nutrigenetics and Nutrigenomics, 4, 36-48.
13. Bouchard, C. (2007). The biological predisposition to obesity: Beyond the thrifty genotype scenario. International Journal of Obesity, 31, 1337-1339.
14. Breen, F.M., Plomin, R. & Wardle, J. (2006). Heritability of food preferences in young children. Physiology & Behavior, 88, 443-447.
15. Buzzetti, R., Petrone, A., Caiazzo, A.M., Alemanno, I., Zavarella, S., Capizzi, M., di Mario, U. (2005). PPAR-gamma2 Pro12Ala variant is associated with greater insulin sensitivity in childhood obesity. Pediatric Research, 57, 138-140.
16. Cai, G., Cole, S.A., Butte, N., Bacino, C., Diego, V., Tan, K., Comuzzie, A.G. (2006). A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children. Obesity, 14, 1596-1604.
17. Carnell, S., Haworth, C.M.A., Plomin, R. & Wardle, J. (2008). Genetic influence on appetite in children. International Journal of Obesity, 32, 1468-1473.
18. Cecil, J., Tavendale, R., Watt, P., Hetherington, M. & Palmer, C. (2008). An obesity-associated FTO gene variant and increased energy intake in children. New England Journal of Medicine, 359, 2558-2566.
19. Cecil, J.E., Fischer, B., Doney, A.S., Hetherington, M., Watt, P., Wrieden, W., Palmer, C.N. (2005). The Pro12Ala and C-681G variants of the PPARG locus are associated with opposing growth phenotypes in young schoolchildren. Diabetologia, 48, 1496-1502.
20. Cecil, J.E., Palmer, C.N.A., Fischer, B., Watt, P., Wallis, D.J., Murrie, I. & Hetherington, M.M. (2007). Variants of the peroxisome proliferator-activated receptor and beta-adrenergic receptor genes are associated with measures of compensatory eating behaviors in young children. American Journal of Clinical Nutrition, 86, 167-173.
21. Chen, T.J., Ji, C.Y., Zheng, X.Y. & Hu, Y.H. (2007). Association of beta3 adrenergic receptor and peroxisome proliferatoractivated receptor gamma 2 polymorphisms with insulin sensitivity: A twin study. Biomedical & Environmental Sciences, 20, 99-105.
22. Clement, K., Vaisse, C., Manning, B.S., Basdevant, A., Guy-Grand, B., Ruiz, J., Strosberg, A.D. (1995). Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. New England Journal of Medicine, 333, 352-354.
23. Clifton, I.J., McDonough, M.A., Ehrismann, D., Kershaw, N.J., Granatino, N. & Schofield, C.J. (2006). Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. Journal of Inorganic Biochemistry, 100, 644-669.
24. Cole, S.A., Butte, N.F., Voruganti, V.S., Cai, G., Haack, K., Kent, J.W., Jr., Gibbs, R.A. (2010). Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children. American Journal of Clinical Nutrition, 91, 191-199.
25. Comings, D.E. & Blum, K. (2000). Reward defi ciency syndrome: Genetic aspects of behavioral disorders. Progress in Brain Research, 126, 325-341.
26. Dahlman, I. & Arner, P. (2010). Genetics of adipose tissue biology. Progress in Molecular Biology and Translational Science, 94, 39-74.
27. Davis, C., Zai, C., Levitan, R.D., Kaplan, A.S., Carter, J.C., Reid-Westoby, C., Kennedy, J.L. (2011). Opiates, overeating and obesity: A psychogenetic analysis. International Journal of Obesity, 35, 1347-1354.
28. De Castro, J.M. (1993). Genetic influences on daily intake and meal patterns of humans. Physiology & Behaviour, 53, 777-782.
29. De Castro, J.M. (2002). Independence of heritable influences on the food intake of free-living humans. Nutrition, 18, 11-16; discussion 91-12.
30. De Luis, D.A., Gonzalez Sagrado, M., Aller, R., Izaola, O. & Conde, R. (2009). Influence of Trp64Arg polymorphism of beta 3-adrenoreceptor gene on insulin resistance, adipocytokines and weight loss secondary to two hypocaloric diets. Annals of Nutrition & Metabolism, 54, 104-110.
31. De Onis, M., Blossner, M., & Borghi, E. (2010). Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr, 92, 1257-1264.
32. Dedoussis, G., Vidra, N., Butler, J., Papoutsakis, C., Yannakoulia, M., Hirschhorn, J.N. & Lyon, H.N. (2009). Peroxisome proliferator- activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity. Clinical Chemistry & Laboratory Medicine, 47, 1047-1050.
33. Dedoussis, G.V., Manios, Y., Kourlaba, G., Kanoni, S., Lagou, V., Butler, J., Lyon, H.N. (2011). An age-dependent dietmodifi ed effect of the PPARgamma Pro12Ala polymorphism in children. Metabolism: Clinical & Experimental, 60, 467-473.
34. Dedoussis, G.V., Theodoraki, E.V., Manios, Y., Yiannakouris, N., Panagiotakos, D., Papoutsakis, C., Zampelas, A. (2007). The Pro12Ala polymorphism in PPARgamma2 gene affects lipid parameters in Greek primary school children: A case of geneto- gender interaction. American Journal of the Medical Sciences, 333, 10-15.
35. Deeb, S.S., Fajas, L., Nemoto, M., Pihlajamaki, J., Mykkanen, L., Kuusisto, J., Auwerx, J. (1998). A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genetics, 20, 284-287.
36. Den Hoed, M., Ekelund, U., Brage, S., Grontved, A., Zhao, J.H., Sharp, S.J., Loos, R.J.F. (2010). Genetic susceptibility to obesity and related traits in childhood and adolescence: Influence of loci identifi ed by genome-wide association studies. Diabetes, 59, 2980-2988.
37. Dina, C., Meyre, D., Gallina, S., Durand, E., Korner, A., Jacobson, P., Froguel, P. (2007). Variation in FTO contributes to childhood obesity and severe adult obesity. Nature Genetics, 39, 724-726.
38. Doney, A., Fischer, B., Frew, D., Cumming, A., Flavell, D.M., World, M., Palmer, C.N. (2002). Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight. BMC Genetics, 3, 21.
39. Doney, A.S., Dannfald, J., Kimber, C.H., Donnelly, L.A., Pearson, E., Morris, A.D. & Palmer, C.N. (2009). The FTO gene is associated with an atherogenic lipid profi le and myocardial infarction in patients with type 2 diabetes: a Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) study. Circulation, Cardiovascular Genetics, 2, 255-259.
40. Doney, A.S., Fischer, B., Cecil, J.E., Boylan, K., McGuigan, F.E., Ralston, S.H., Palmer, C.N. (2004). Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. Diabetologia, 47, 555-558.
41. Dubois, L., Ohm Kyvik, K., Girard, M., Tatone-Tokuda, F., Perusse, D., Hjelmborg, J., Martin, N.G. (2012). Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: An international study of over 12,000 twin pairs. PLoS One, 7, e30153.
42. Ellsworth, D.L., Coady, S.A., Chen, W., Srinivasan, S.R., Elkasabany, A., Gustat, J., Berenson, G.S. (2002). Influence of the beta2- adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. International Journal of Obesity and Related Metabolic Disorders, 26, 928-937.
43. Emorine, L., Blin, N. & Strosberg, A.D. (1994). The human beta 3-adrenoceptor: the search for a physiological function. Trends in Pharmacological Science, 15, 3-7.
44. Endo, K., Yanagi, H., Hirano, C., Hamaguchi, H., Tsuchiya, S. & Tomura, S. (2000). Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity. International Journal of Obesity & Related Metabolic Disorders, 24, 443-449.
45. Epstein, L.H., Dearing, K.K. & Erbe, R.W. (2010). Parent-child concordance of Taq1 A1 allele predicts similarity of parent-child weight loss in behavioral family-based treatment programs. Appetite, 55, 363-366.
46. Erhardt, E., Czako, M., Csernus, K., Molnar, D. & Kosztolanyi, G. (2005). The frequency of Trp64Arg polymorphism of the beta 3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors. European Journal of Clinical Nutrition, 59, 955-959.
47. Evans, R.M., Barish, G.D. & Wang, Y.X. (2004). PPARs and the complex journey to obesity. Nature Medicine, 10, 355-361.
48. Faith, M.S., Keller, K.L., Johnson, S.L., Pietrobelli, A., Matz, P.E., Must, S., Allison, D.B. (2004). Familial aggregation of energy intake in children. American Journal of Clinical Nutrition, 79, 844-850.
49. Faith, M.S., Pietrobelli, A., Nunez, C., Heo, M., Heymsfield, S.B. & Allison, D.B. (1999). Evidence for independent genetic influences on fat mass and body mass index in a pediatric twin sample. Pediatrics, 104, 61-67.
50. Falciglia, G.A. & Norton, P.A. (1994). Evidence for a genetic influence on preference for some foods. Journal of the American Dietetic Association, 94, 154-158.
51. Fang, H., Li, Y., Du, S., Hu, X., Zhang, Q., Liu, A. & Ma, G. (2010). Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children. BMC Medical Genetics, 11, 136.
52. Farooqi, I.S., Keogh, J.M., Yeo, G.S.H., Lank, E.J., Cheetham, T. & O ' Rahilly, S. (2003). Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. New England Journal of Medicine, 348, 1085-1095.
53. Farooqi, I.S. & O ' Rahilly, S. (2005). Monogenic obesity in humans. Annual Review of Medicine, 56, 443-458.
54. Ferreira, A.P., Oliveira, C.E. & Franca, N.M. (2007). Metabolic syndrome and risk factors for cardiovascular disease in obese children: The relationship with insulin resistance (HOMA-IR). Jornal de Pediatria, 83, 21-26.
55. Finlayson, G., King, N. & Blundell, J.E. (2007). Liking vs wanting food: Importance for human appetite control and weight regulation. Neuroscience & Biobehavioral Reviews, 31, 987-1002.
56. Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Bruning, J.C. & Ruther, U. (2009). Inactivation of the FTO gene protects from obesity. Nature, 458, 894-898.
57. Fisher, J.O., Cai, G., Jaramillo, S.J., Cole, S.A., Comuzzie, A.G. & Butte, N.F. (2007). Heritability of hyperphagic eating behavior and appetite-related hormones among hispanic children. Obesity, 15, 1484-1495.
58. Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., McCarthy, M.I. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316, 889-894.
59. Fredriksson, R., Hagglund, M., Olszewski, P.K., Stephansson, O., Jacobsson, J.A., Olszewska, A.M., Schioth, H.B. (2008). The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology, 149, 2062-2071.
60. Galvao, A.C., Kruger, R.C., Campagnolo, P.D., Mattevi, V.S., Vitolo, M.R. & Almeida, S. (2012). Association of MAOA and COMT gene polymorphisms with palatable food intake in children. Journal of Nutritional Biochemistry, 23, 272-277.
61. Gearing, K.L., Gottlicher, M., Widmark, E., Banner, C.D., Tollet, P., Stromstedt, M., Gustafsson, J.A. (1994). Fatty acid activation of the peroxisome proliferator activated receptor, a member of the nuclear receptor gene superfamily. Journal of Nutrition, 124, S1284-S1288.
62. Gerken, T., Girard, C.A., Tung, Y.C., Webby, C.J., Saudek, V., Hewitson, K.S., Schofield, C.J. (2007). The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 318, 1469-1472.
63. Grant, S.F., Li, M., Bradfield, J.P., Kim, C.E., Annaiah, K., Santa, E., Hakonarson, H. (2008). Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS One, 3, e1746.
64. Hakanen, M., Raitakari, O.T., Lehtimaki, T., Peltonen, N., Pahkala, K., Sillanmaki, L., Ronnemaa, T. (2009). FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. Journal of Clinical Endocrinology and Metabolism, 94, 1281-1287.
65. Hamann, A., Munzberg, H., Buttron, P., Busing, B., Hinney, A., Mayer, H., Greten, H. (1999). Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects. European Journal of Endocrinology, 141, 90-92.
66. Hardy, R., Wills, A.K., Wong, A., Elks, C.E., Wareham, N.J., Loos, R.J., Ong, K.K. (2010). Life course variations in the associations between FTO and MC4R gene variants and body size. Human Molecular Genetics, 19, 545-552 .
67. Haupt, A., Thamer, C., Staiger, H., Tschritter, O., Kirchhoff, K., Machicao, F., Fritsche, A. (2009). Variation in the FTO gene influences food intake but not energy expenditure. Experimental & Clinical Endocrinology & Diabetes, 117, 194-197.
68. Haworth, C.M., Butcher, L.M., Docherty, S.J., Wardle, J. & Plomin, R. (2008a). No evidence for association between BMI and 10 candidate genes at ages 4, 7 and 10 in a large UK sample of twins. BMC Medical Genetics, 9, 12.
69. Haworth, C.M.A., Carnell, S., Meaburn, E.L., Davis, O.S.P., Plomin, R. & Wardle, J. (2008b). Increasing heritability of BMI and stronger associations with the FTO gene over childhood. Obesity, 16, 2663-2668.
70. Heard-Costa, N.L., Zillikens, M.C., Monda, K.L., Johansson, A., Harris, T.B., Fu, M., North, K.E. (2009). NRXN3 is a novel locus for waist circumference: A genome-wide association study from the CHARGE consortium. PLoS Genetics, 5, e1000539.
71. Hinney, A., Lentes, K.U., Rosenkranz, K., Barth, N., Roth, H., Ziegler, A., Hebebrand, J. (1997). Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa. International Journal of Obesity & Related Metabolic Disorders, 21, 224-230.
72. Hsiao, G., Chapman, J., Ofrecio, J.M., Wilkes, J., Resnik, J.L., Thapar, D., Sears, D.D. (2011). Multi-tissue, selective PPARgamma modulation of insulin sensitivity and metabolic pathways in obese rats. American Journal of Physiology: Endocrinology & Metabolism, 300, E164-174.
73. Hsueh, W.C., Cole, S.A., Shuldiner, A.R., Beamer, B.A., Blangero, J., Hixson, J.E., Mitchell, B.D. (2001). Interactions between variants in the beta3-adrenergic receptor and peroxisome proliferator- activated receptor-gamma2 genes and obesity. Diabetes Care, 24, 672-677.
74. Keskitalo, K., Tuorila, H., Spector, T.D., Cherkas, L.F., Knaapila, A., Kaprio, J., Perola, M. (2008). The Three-Factor Eating Questionnaire, body mass index, and responses to sweet and salty fatty foods: A twin study of genetic and environmental associations. American Journal of Clinical Nutrition, 88, 263-271.
75. Kilpelainen, T.O., Qi, L., Brage, S., Sharp, S.J., Sonestedt, E., Demerath, E., Loos, R.J. (2011). Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children. PLoS Medicine, 8, e1001116.
76. Krief, S., Lonnqvist, F., Raimbault, S., Baude, B., Van Spronsen, A., Arner, P., Emorine, L.J. (1993). Tissue distribution of beta 3-adrenergic receptor mRNA in man. Journal of Clinical Investigation, 91, 344-349.
77. Kurokawa, N., Nakai, K., Kameo, S., Liu, Z.-M. & Satoh, H. (2003). Relationship between the beta3-adrenoceptor gene variant and body fat in Japanese children. Tohoku Journal of Experimental Medicine, 201, 271-276.
78. Lagou, V., Liu, G., Zhu, H., Stallmann-Jorgensen, I.S., Gutin, B., Dong, Y. & Snieder, H. (2011). Lifestyle and socioeconomicstatus modify the effects of ADRB2 and NOS3 on adiposity in European-American and African-American adolescents. Obesity, 19, 595-603.
79. Lagou, V., Scott, R.A., Manios, Y., Chen, T.L.J., Wang, G., Grammatikaki, E., Pitsiladis, Y.P. (2008). Impact of peroxisome proliferator-activated receptors and on adiposity in toddlers and preschoolers in the GENESIS study. Obesity, 16, 913-918.
80. Lajunen, H.R., Kaprio, J., Keski-Rahkonen, A., Rose, R.J., Pulkkinen, L., Rissanen, A. & Silventoinen, K. (2009). Genetic and environmental effects on body mass index during adolescence: A prospective study among Finnish twins. International Journal of Obesity, 33, 559-567.
81. Lee, H.J., Kim, I.K., Kang, J.H., Ahn, Y., Han, B.G., Lee, J.Y. & Song, J. (2010). Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans. Clinica Chimica Acta, 411, 1716-1722.
82. Lillycrop, K.A. & Burdge, G.C. (2011). Epigenetic changes in early life and future risk of obesity. International Journal of Obesity, 35, 72-83.
83. Lima, J.J., Feng, H., Duckworth, L., Wang, J., Sylvester, J.E., Kissoon, N. & Garg, H. (2007). Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism, 56, 757-765.
84. Llewellyn, C.H., van Jaarsveld, C.H.M., Boniface, D., Carnell, S. & Wardle, J. (2008). Eating rate is a heritable phenotype related to weight in children. American Journal of Clinical Nutrition, 88, 1560-1566.
85. Loos, R.J. & Bouchard, C. (2008). FTO: The first gene contributing to common forms of human obesity. Obesity Reviews, 9, 246-250.
86. Loos, R.J., Lindgren, C.M., Li, S., Wheeler, E., Zhao, J.H., Prokopenko, I., Mohlke, K.L. (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics, 40, 768-775.
87. Luan, J., Browne, P.O., Harding, A.H., Halsall, D.J., O ' Rahilly, S., Chatterjee, V.K. & Wareham, N.J. (2001). Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes, 50, 686-689.
88. Lutter, M. & Nestler, E.J. (2009). Homeostatic and hedonic signals interact in the regulation of food intake. Journal of Nutrition, 139, 629-632.
89. Maes, H.H., Neale, M.C. & Eaves, L.J. (1997). Genetic and environmental factors in relative body weight and human adiposity. Behavior Genetics, 27, 325-351.
90. Marti, A., Corbalan, M.S., Martinez-Gonzalez, M.A., Forga, L. & Martinez, J.A. (2002). CHO intake alters obesity risk associated with Pro12Ala polymorphism of PPARgamma gene. Journal of Physiology & Biochemistry, 58, 219-220.
91. Marti, A., Corbalan, M.S., Martinez-Gonzalez, M.A. & Martinez, J.A. (2002). TRP64ARG polymorphism of the beta 3-adrenergic receptor gene and obesity risk: effect modifi cation by a sedentary lifestyle. Diabetes, Obesity & Metabolism, 4, 428-430.
92. Meirhaeghe, A., Fajas, L., Gouilleux, F., Cottel, D., Helbecque, N., Auwerx, J. & Amouyel, P. (2003). A functional polymorphism in a STAT5B site of the human PPAR gamma 3 gene promoter affects height and lipid metabolism in a French population. Arteriosclerosis, Thrombosis & Vascular Biology, 23, 289-294.
93. Meirhaeghe, A., Fajas, L., Helbecque, N., Cottel, D., Lebel, P., Dallongeville, J., Amouyel, P. (1998). A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans. Human Molecular Genetics, 7, 435-440.
94. Memisoglu, A., Hu, F.B., Hankinson, S.E., Manson, J.E., De Vivo, I., Willett, W.C. & Hunter, D.J. (2003). Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass. Human Molecular Genetics, 12, 2923-2929.
95. Nadeau, K.J., Maahs, D.M., Daniels, S.R. & Eckel, R.H. (2011). Childhood obesity and cardiovascular disease: Links and prevention strategies. Nature Reviews Cardiology, 8, 513-525.
96. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. (1991). Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Archives of General Psychiatry, 48, 648-54.
97. Ochoa, M.C., Marti, A., Azcona, C., Chueca, M., Oyarzabal, M., Pelach, R., Groupo de Estudio Navarro de Obesidad, I. (2004). Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. International Journal of Obesity & Related Metabolic Disorders, 28, S37-41.
98. Okuda, M., Hinoda, Y., Okayama, N., Suehiro, Y., Shirabe, K., Sasaki, S., Hobara, T. (2011). Association between the FTO gene and overweight in Japanese children and adolescents. Pediatric Diabetes, 12, 494-500.
99. Park, H.S., Kim, Y. & Lee, C. (2005). Single nucleotide variants in the beta2-adrenergic and beta3-adrenergic receptor genes explained 18.3% of adolescent obesity variation. Journal of Human Genetics, 50, 365-369.
100. Perusse, L., Leblanc, C. & Bouchard, C. (1988). Familial resemblance in lifestyle components: results from the Canada Fitness Survey. Canadian Journal of Public Health, 79, 201-205.
101. Pierola, J., Barcelo, A., de la Pena, M., Barbe, F., Soriano, J.B., Sanchez Armengol, A., Agusti, A. (2007). beta3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea. European Respiratory Journal, 30, 743-747.
102. Pihlajamaki, J., Vanhala, M., Vanhala, P. & Laakso, M. (2004). The Pro12Ala polymorphism of the PPAR gamma 2 gene regulates weight from birth to adulthood. Obesity Research, 12, 187-190.
103. Rankinen, T. & Bouchard, C. (2006). Genetics of food intake and eating behavior phenotypes in humans. Annual Review of Nutrition, 26, 413-434.
104. Rendo, T., Moleres, A. & Marti Del Moral, A. (2009). Effects of the FTO gene on lifestyle intervention studies in children. Obesity Facts, 2, 393-399.
105. Rosado, E.L., Bressan, J., Martinez, J.A. & Marques-Lopes, I. (2010). Interactions of the PPARgamma2 polymorphism with fat intake affecting energy metabolism and nutritional outcomes in obese women. Annals of Nutrition & Metabolism, 57, 242-250.
106. Rosado, E.L., Bressan, J., Martins, M.F., Cecon, P.R. & Martinez, J.A. (2007). Polymorphism in the PPARgamma2 and beta2-adrenergic genes and diet lipid effects on body composition, energy expenditure and eating behavior of obese women. Appetite, 49, 635-643.
107. Rosen, E.D., Hsu, C.H., Wang, X., Sakai, S., Freeman, M.W., Gonzalez, F.J. & Spiegelman, B.M. (2002). C/EBPalpha induces adipogenesis through PPARgamma: a unifi ed pathway. Genes & Development, 16, 22-26.
108. Rutters, F., Nieuwenhuizen, A.G., Bouwman, F., Mariman, E. & Westerterp-Plantenga, M.S. (2011). Associations between a single nucleotide polymorphism of the FTO gene (rs9939609) and obesity-related characteristics over time during puberty in a Dutch children cohort. Journal of Clinical Endocrinology & Metabolism, 96, E939-942.
109. Rzehak, P., Scherag, A., Grallert, H., Sausenthaler, S., Koletzko, S., Bauer, C.P., Group, L.S. (2010). Associations between BMI and the FTO gene are age dependent: Results from the GINI and LISA birth cohort studies up to age 6 years. Obesity Facts, 3, 173-180.
110. Salsberry, P.J. & Reagan, P.B. (2010). Effects of heritability, shared environment, and nonshared intrauterine conditions on child and adolescent BMI. Obesity, 18 (9), 1775-1780.
111. Scaglioni, S., Verduci, E., Salvioni, M., Biondi, M.L., Radaelli, G., Agostoni, C. & Giovannini, M. (2006). PPAR-gamma2 Pro12Ala variant, insulin resistance and plasma long-chain polyunsaturated fatty acids in childhood obesity. Pediatric Research, 60, 485-489.
112. Scott, R.A., Bailey, M.E.S., Moran, C.N., Wilson, R.H., Fuku, N., Tanaka, M., Pitsiladis, Y.P. (2010). FTO genotype and adiposity in children: Physical activity levels influence the effect of the risk genotype in adolescent males. European Journal of Human Genetics, 18, 1339-1343.
113. Scuteri, A., Sanna, S., Chen, W.M., Uda, M., Albai, G., Strait, J., Abecasis, G.R. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesityrelated traits. PLoS Genetics, 3, e115.
114. Small, D.M., Jones-Gotman, M. & Dagher, A. (2003). Feedinginduced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroimage, 19, 1709-1715.
115. Sovio, U., Mook-Kanamori, D.O., Warrington, N.M., Lawrence, R., Briollais, L., Palmer, C.N., Early Growth Genetics Consortium (2011). Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development. PLoS Genetics, 7, e1001307.
116. Speakman, J.R. (2010). FTO effect on energy demand versus food intake. Nature, 464, E1; discussion E2.
117. Speakman, J.R., Rance, K.A. & Johnstone, A.M. (2008). Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity, 16, 1961-1965.
118. Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A.U., Loos, R.J. (2010). Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics, 42, 937-948.
119. Spiegelman, B.M. (1998). PPAR-gamma: Adipogenic regulator and thiazolidinedione receptor. Diabetes, 47, 507-514.
120. Stice, E., Spoor, S., Bohon, C. & Small, D.M. (2008). Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science, 322, 449-452.
121. Stice, E., Yokum, S., Bohon, C., Marti, N. & Smolen, A. (2010). Reward circuitry responsivity to food predicts future increases in body mass: Moderating effects of DRD2 and DRD4. Neuroimage, 50, 1618-1625.
122. Stratigopoulos, G., Padilla, S.L., LeDuc, C.A., Watson, E., Hattersley, A.T., McCarthy, M.I., Leibel, R.L. (2008). Regulation of FTO/FTM gene expression in mice and humans. American Journal of Physiology: Regulatory Integrative & Comparative Physiology, 294, R1185-1196.
123. Stutzmann, F., Cauchi, S., Durand, E., Calvacanti-Proenca, C., Pigeyre, M., Hartikainen, A.L., Froguel, P. (2009). Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. International Journal of Obesity, 33, 373-378.
124. Su, A.I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K.A., Block, D., Hogenesch, J.B. (2004). A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences of the United States of America, 101, 6062-6067.
125. Sung, J., Lee, K., Song, Y.M., Lee, M.K. & Lee, D.H. (2010). Heritability of eating behavior assessed using the DEBQ (Dutch Eating Behavior Questionnaire) and weight-related traits: the Healthy Twin Study. Obesity, 18, 1000-1005.
126. Tafel, J., Branscheid, I., Skwarna, B., Schlimme, M., Morcos, M., Algenstaedt, P., Hamann, A. (2004). Variants in the human beta1-, beta2- and beta3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents. Diabetes, Obesity and Metabolism, 6, 452-455.
127. Tanofsky-Kraff, M., Han, J.C., Anandalingam, K., Shomaker, L.B., Columbo, K.M., Wolkoff, L.E., Yanovski, J.A. (2009). The FTO gene rs9939609 obesity-risk allele and loss of control over eating. American Journal of Clinical Nutrition, 90, 1483-1488.
128. Temple, J.L., Legierski, C.M., Giacomelli, A.M., Salvy, S.J. & Epstein, L.H. (2008). Overweight children fi nd food more reinforcing and consume more energy than do nonoverweight children. American Journal of Clinical Nutrition, 87, 1121-1127.
129. Timpson, N.J., Emmett, P.M., Frayling, T.M., Rogers, I., Hattersley, A.T., McCarthy, M.I. & Davey Smith, G. (2008). The fat mass- and obesity-associated locus and dietary intake in children. American Journal of Clinical Nutrition, 88, 971-978.
130. Tonjes, A., Scholz, M., Loeffler, M. & Stumvoll, M. (2006). Association of Pro12Ala polymorphism in peroxisome proliferatoractivated receptor gamma with pre-diabetic phenotypes: Meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care, 29, 2489-2497.
131. Tschritter, O., Preissl, H., Yokoyama, Y., Machicao, F., Haring, H.U. & Fritsche, A. (2007). Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans. Diabetologia, 50, 2602-2603.
132. Valladares, M., Dominguez-Vasquez, P., Obregon, A.M., Weisstaub, G., Burrows, R., Maiz, A. & Santos, J.L. (2010). Melanocortin-4 receptor gene variants in Chilean families: association with childhood obesity and eating behavior. Nutritional Neuroscience, 13, 71-78.
133. Valve, R., Sivenius, K., Miettinen, R., Pihlajamaki, J., Rissanen, A., Deeb, S.S., Laakso, M. (1999). Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women. Journal of Clinical Endocrinology & Metabolism, 84, 3708-3712.
134. Van Strien, T., Snoek, H.M., van der Zwaluw, C.S. & Engels, R.C.M.E. (2010). Parental control and the dopamine D2 receptor gene (DRD2) interaction on emotional eating in adolescence. Appetite, 54, 255-261.
135. Vidal-Puig, A., Jimenez-Linan, M., Lowell, B.B., Hamann, A., Hu, E., Spiegelman, B., Moller, D.E. (1996). Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. Journal of Clinical Investigation, 97, 2553-2561.
136. Vidal-Puig, A.J., Considine, R.V., Jimenez-Linan, M., Werman, A., Pories, W.J., Caro, J.F. & Flier, J.S. (1997). Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. Journal of Clinical Investigation, 99, 2416-2422.
137. Volkow, N.D., Wang, G.J., Telang, F., Fowler, J.S., Thanos, P.K., Logan, J., Pradhan, K. (2008). Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors. Neuroimage, 42, 1537-1543.
138. Wang, G., Volkow, N.D., Logan, J., Pappas, N.R., Wong, C.T., Zhu, W., Fowler, J.S. (2001). Brain dopamine and obesity. Lancet, 357, 354-357.
139. Wang, X.L., Oosterhof, J. & Duarte, N. (1999). Peroxisome proliferator-activated receptor gamma C161 ? T polymorphism and coronary artery disease. Cardiovascular Research, 44, 588-594.
140. Wardle, J., Carnell, S., Haworth, C.M. & Plomin, R. (2008a). Evidence for a strong genetic influence on childhood adiposity despite the force of the
141. Wardle, J., Carnell, S., Haworth, C. M. A., Farooqi, I. S., O'Rahilly, S., & Plomin, R. (2008b). Obesity associated genetic variation in FTO is associated with diminished satiety. Journal of Clinical Endocrinology and Metabolism, 93, 3640-3643.
142. Wardle, J., Llewellyn, C., Sanderson, S. & Plomin, R. (2009). The FTO gene and measured food intake in children. International Journal of Obesity, 33, 42-45.
143. Whitaker, R.C., Pepe, M.S., Wright, J.A., Seidel, K.D. & Dietz, W.H. (1998). Early adiposity rebound and the risk of adult obesity. Pediatrics, 101, E5.
144. Widen, E., Lehto, M., Kanninen, T., Walston, J., Shuldiner, A.R. & Groop, L.C. (1995). Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. New England Journal of Medicine, 333, 348-351.
145. Wiegand, S., Dannemann, A., Krude, H. & Gruters, A. (2005). Impaired glucose tolerance and type 2 diabetes mellitus: A new field for pediatrics in Europe. International Journal of Obesity, 29, S136-142.
146. Willer, C. J., Speliotes, E. K., Loos, R. J., Li, S., Lindgren, C. M., Heid, I. M., Hirschhorn, J. N. (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet, 41, 25-34.
147. Wright, C.M., Cox, K.M. & Le Couteur, A. (2011). How does infant behaviour relate to weight gain and adiposity? Proceedings of the Nutrition Society, 70, 485-493.
148. Xi, B., Shen, Y., Zhang, M., Liu, X., Zhao, X., Wu, L., Wang, X. (2010). The common rs9939609 variant of the fat mass and obesity- associated gene is associated with obesity risk in children and adolescents of Beijing, China. BMC Medical Genetics, 11, 107
149. Xinli, W., Xiaomei, T., Meihua, P. & Song, L. (2001). Association of a mutation in the beta3-adrenergic receptor gene with obesity and response to dietary intervention in Chinese children. Acta Paediatrica, 90, 1233-1237.
150. Zhang, B., Graziano, M.P., Doebber, T.W., Leibowitz, M.D., White-Carrington, S., Szalkowski, D.M., Smith, R.G. (1996). Down-regulation of the expression of the obese gene by an antidiabetic thiazolidinedione in Zucker diabetic fatty rats and db/db mice. J Biol Chem, 271, 9455-9459.
151. Zimmet, P., Alberti, G., Kaufman, F., Tajima, N., Silink, M., Arslanian, S., Caprio, S. (2007). The metabolic syndrome in children and adolescents. Lancet, 369, 2059-2061.