Reward Deficiency Syndrome in Children: Obesity and Metabolic Disorders are Associated with the SNP TaqIA C32806T of the DRD2 Gene
DOI:
https://doi.org/10.17140/OROJ-2-111Keywords:
Childhood obesity; DRD2 gene; HOMA; Dopamine; Genetic polymorphismAbstract
Background: Reward Deficiency Syndrome (RDS) is a hypo-dopaminergic state that predisposes to obsessive-compulsive behaviors. Obesity is part of RDS since the individual is predisposed to reward-driven eating behavior that leads to overeating. The allele A1 of the SNP
C32806T in Dopamine D2 receptor gene (DRD2) is associated with reduction of DRD2 levels
and higher BMI in adults. DRD2 are expressed in beta cells and modulate insulin secretion.
The aim of this study is to investigate the relation between this SNP and obesity and metabolic
alterations in children.
Methods: Fifty five obese children and 50 healthy controls were analyzed for DRD2 Taq1A
polymorphism Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. Glucose, insulin and lipid profile were measured. The Homeostatic
model assessment (HOMA) was calculated.
Results: We found three genotypes: A1A1(12,4%), A1A2(33,3%) and A2A2(54,3%). The A1
allele was more present in: obese than in euthrophic (34,5%*23%), in children with altered
HOMA ß (38,2% * 24,6%), children with altered Total Cholesterol (35,2%*19,5%) and lower
levels of triglycerides. Children were divided in 4 subgroups in accordance to the function of
pancreatic beta cells and BMI-Z; subgroups with normal secreting pancreatic beta cell demonstrated significant difference for allelic and genotypic distribution, with lower presence of
A1A1 and A1A2 genotypes and higher presence of A2 allele.
Conclusions: Besides confirming the association with childhood obesity, our results show for
the first time that: A1 allele is associated with TC≥170 mg/dl, lower TG levels and HOMA ß
≥175. A2 allele is associated with normal HOMA ß, being a protective factor for pancreatic
secretion. The recognition of predisposed individuals through determinations of risks polymorphisms can lead to new paths for treatment and prevention of metabolic abnormalities.
References
World Health Organization. Obesity preventing and manag-ing the global epidemic; Report of a WHO Consultation (WHO Technical report series 894). Geneve, WHO. 2000; 252.
Bell CG, Walley AW, Frogue lP. The genetics of human obe-sity. Nature Reviews Genetics. 2005; 6: 221-234. doi: 10.1038/ nrg1556
Keats S, Wiggins S. Future diets: Obesity is on the rise glob-ally. Website: http://www.odi.org.uk/future-diets, 2014.
Amemiya S, Dobashi K, Urakami T, Sugihara S, Ohzeki T, Tajima N. Metabolic syndrome in youths. Pediatric Diabetes. 2007; 8: 48-54. doi: 10.1111/j.1399-5448.2007.00226.x
Radominski RB. Epidemiological aspects of childhood obe-sity. Revista ABESO. 2011; 49: 10-13.
Demerath EW, Choh AC, Czerwinski SA, et al. Genetics and environmental influences on infant weight and weight change: the FELS Longitudinal Study. Am J Hum Biol. 2007; 19: 692- 702.
Griffiths LJ, Dezateux C, Cole TJ. Differential parental weight and height contributions to offspring birthweight and weight gain in infancy. Int J Epidemiol. 2007; 36: 104-107. doi: 10.1093/ije/dyl210
Bradfield JP, Taal HR, Timpson NJ, et al. A genome-wide as-sociation meta-analysis identifies new childhood obesity loci. Nature Genetics. 2012; 44: 526-531. doi: 10.1038/ng.2247
Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyro-poulos G, Walts B. The human obesity gene map: the 2005 up-date. Obes Res. 2006; 14: 529–644. doi: 10.1038/oby.2006.71
Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat. 2004; 23: 540-545. doi: 10.1002/humu.20039
Huang XF, Zavitsanou K, Huang X, et al. Dopamine trans-porter and D2 receptor binding densities in mice prone or resis-tant to chronic high fat diet-incuded obesity. Behav Brain Res. 2006; 175: 415-419. doi: 10.1016/j.bbr.2006.08.034
Wang GJ, Volkow ND, Logan J, et al. Brain dopamine and obesity. The lancet. 2001; 3: 354-357. doi: 10.1016/S0140- 6736(00)03643-6
Blum K, Braverman ER, Wood RC, et al. Increased prev-alence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a pre-liminary report. Pharmacogenetics. 1996; 6: 297-305.
Nisoli E, Brunani A, Borgomainerio E, et al. D2 dopamine receptor (DRD2) gene Taq1A polymorphism and the eating-re-lated psychological traits in eating disorders (anorexia nervosa and bulimia) and obesity. Eat Weight Disord. 2007; 12: 91-95. 10.1007/BF03327583
Chen AL, Blum K, Chen TJ, et al. Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. Food Funct. 2012; 3: 40-48. doi: 10.1039/c1fo10089k
Kukreti R, Tripathi S, Bhatnagar P, et al. Association of DRD2 gene variant with schizophrenia. Neurosci Lett. 2005; 392: 68-71. doi: 10.1016/j.neulet.2005.08.059
Jönsson EG, Nöthen MM, Gründhage F, et al. Polymor-phisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry. 1999; 4: 290-296.
Noble EP, Gottschalk LA, Fallon JH, Ritchie TL, Wu JC. D2 dopamine receptor polymorphism and brains re-gional glucose metabolism. Am J Med Genet B Neuropsy-chiatr Genet. 1997; 7: 162-166. doi: 10.1002/(SICI)1096- 8628(19970418)74:2<162::AID-AJMG9>3.0.CO;2-W
Blum K, Chen ALC, Giordano J, et al. The addictive brain: all roads lead to dopamine. Journal of Psychoactive Drugs. 2012; 44: 134-143. doi: 10.1080/02791072.2012.685407
Blum K, Cull J, Braverman ER, Comings D. Reward defi-ciency syndrome. American Scientist. 1996; 84: 132-145.
World Health Organization. WHO Expert Comitee on Physi-cal Status: the use and interpretation of antropometry and physi-cal status (WHO Technical Report Series, 854). Geneve, WHO. 1995; 452.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treach-er DF, Turner RC. Homeostasis model assessment: insulin re-sistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28: 412-419.
Araz NC, Nacak M, Balci SO, et al. Childhood obesity and the role of dopamine D2 receptor and cannabinoid receptor-1 gene polymorphisms. Genetic Testing and Molecular Biomark-ers. 2012; 16: 1408-1412. doi: 10.1089/gtmb.2012.0244
Brazilian Society of Cardiology. Atherosclerosis Prevention Guidelines in Childhood and Adolescence. Brazilian Archives of Cardiology. 2005; 85: 1-36.
Metcalf NS, Hosking J, Fremeaux AE, Jeffery AN, Voss LD, Wilkin TJ. BMI was right all along-taller childen really are fatter 3 implications of making childhood BMI independent of height. Int J Obes. 2011; 35: 541-547. doi: 10.1038/ijo.2010.258
Bouchard C, Perusse L, Rice T, Rao DC. The genetics of human obesity; In: Dekker M, ed. Handbook of Obesity, New York, Bray G, 1998; 157-190.
Rankinen T, Perusse L, Weisnagel SJ, Snyder EE, Chagnon YC, Bouchard C. The human obesity gene map: the 2001 up-date. Obes Res. 2002; 10: 196-243.
Hainer V, ZamrazilováH, Spálová J, et al. Role of Hereditary Factors in Weight Loss and Its Maintenance. Physiol. Res. 2008; 57: S1-S15.
Fisberg M, Cintra IP, Costa RF. Obese children and ado-lescents: epidemiology, diagnosis, body composition and treat-ment. In: Setian N, ed. Obesity in children and adolescents. São Paulo, Roca. 2007; 7-28.
Brazilian Institute of Geography and Statistics. Family Bud-get Survey (POF) 2008-2009- anthropometry and nutritional sta-tus of children, adolescents and adults in Brazil. In: de Janeiro R, ed. IBGE. 2010; 1-130.
Noble EP, Blum K, Ritchie T, Montgomery A, Sheri-dan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Archives of general Psychiatry. 1991; 48: 648-654. doi: 10.1001/arch-psyc.1991.01810310066012
Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010; 50: 1618-1625. doi: 10.1016/j.neuroimage.2010.01.081
Böettcher Y, Korner A, Kovacs P, Kiess P. Obesity genes: implication in childhood obesity. Pediatrics and child health. 2011; 22: 31-36. doi: 10.1016/j.paed.2011.08.009
Ergun MA, Karaoguz MY, Koc A, et al. The apolipoprotein E gene and Taq1A polymorphisms in childhood obesity. Genet-ic Testing and Molecular Biomarkers. 2010; 14: 343-345. doi: 10.1089/gtmb.2010.0002
Strien T, Snoek HM, van der Zwaluw C, Engels RC. Parental control and the dopamine D2 receptor gene (DRD2) interaction on emotional eating in adolescence. Appetite. 2010; 54: 255- 261. doi: 10.1016/j.appet.2009.11.006
Roth CL, Hinne A, Schur EA, Elfers CT, Reinehr T. Associa-tion analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention. BMC Pediatrics. 2013; 13: 197- 205. doi: 10.1186/1471-2431-13-197
Duran-Gonzalez J, Ortiz I, Gonzales E, et al. Association study of candidate gene polymorphisms and obesity in a young mexican-american population from South Texas. Arch Med Re-search. 2011; 42: 523-531. doi: 10.1016/j.arcmed.2011.10.010
Miyashita M, Burns SF, Stensel DJ. An update on accumu-lating exercise and postprandial lipaemia: translating theory into practice. J Prev med Public Health. 2013; 46: S3-S11. doi: 10.3961/jpmph.2013.46.S.S3
Lee HJ, Lee HS, Kim YK, et al. D2 and D4 dopamine recep-tor gene polymorphisms and personality traits in a young Kore-an population. Am J Med Genet B Neuropsychiatr Genet. 2003; 121B: 44-49. doi: 10.1002/ajmg.b.20054
Noble EP, Ozkaragoz TZ, Ritchie TL, Zhang X, Belin TR, Sparkes RS. D2 and D4 dopamine receptor polymorphisms and personality. Am J Med Genetics. 1998; 81: 257-267. doi: 10.1002/ (SICI)1096-8628(19980508)81:3<257::AID-AJMG10> 3.0.CO;2-E
Noble EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Gene. 2003; 116: 103-125. doi: 10.1002/ajmg.b.10005
Wang TY, Lee SY, Chen SL, et al. Association between DRD2, 5-HTTLPR, and ALDH2 genes and specific personal-ity traits in alcohol- and opiate-dependent patients. Behav Brain Res. 2013; 250: 285-292. doi: 10.1016/j.bbr.2013.05.015
Pijl H, Ohashi S, Matsuda M, et al. Bromocriptine a novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000; 23: 1154-1160. doi: 10.2337/diacare.23.8.1154
WeenenJEL, Parlevliet ET, Maechler P, et al. The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of α2-adrenergic receptors in beta cells. Biochemical Pharmacology. 2010; 79: 1827-1836. doi: 10.1016/j.bcp.2010.01.029
Rubi B, Ljubicic S, Pournourmohammadi S, et al. Dopamine D2-like receptors are expressed in pancreatic beta cells and me-diate inhibition of insulin secretion. Journal of Biological Chem-istry. 2005; 280: 36824-36832. doi: 10.1074/jbc.M505560200
García-Tornadú I, Ornstein AM, Chamson-Reig A, et al. Disruption of the dopamine D2 receptor impairs insulin secre-tion and causes glucose intolerance. Endocrinology. 2010; 151: 1441-1450. doi: 10.1210/en.2009-0996
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Obesity Research (OR) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.
