Reward Deficiency Syndrome in Children: Obesity and Metabolic Disorders are Associated with the SNP TaqIA C32806T of the DRD2 Gene

Abstract

Citation ResearchPage 64 ABSTRACT 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.