RESUMEN
Food reinforcement, or the motivation to eat, has been associated with increased energy intake, greater body weight, and prospective weight gain. Much of the previous research on the reinforcing value of food has focused on the role of dopamine, but it may be worthwhile to examine genetic polymorphisms in the serotonin and opioid systems as these neurotransmitters have been shown to be related to reinforcement processes and to influence energy intake. We examined the relationship among 44 candidate genetic polymorphisms in the dopamine, serotonin, and opioid systems, as well as food reinforcement and body mass index (BMI) in a sample of 245 individuals. Polymorphisms in the monoamine oxidase A (MAOA-LPR) and serotonin receptor 2A genes (rs6314) moderated the effect of food reinforcement on BMI, accounting for an additional 5-10% variance and revealed a potential role of the single nucleotide polymorphism, rs6314, in the serotonin 2A receptor as a differential susceptibility factor for obesity. Differential susceptibility describes a factor that can confer either risk or protection depending on a second variable, such that rs6314 is predictive of both high and low BMI based on the level of food reinforcement, while the diathesis stress or dual-gain model only influences one end of the outcome measure. The interaction with MAOA-LPR better fits the diathesis stress model, with the 3.5R/4R allele conferring protection for individuals low in food reinforcement. These results provide new insight into genes theoretically involved in obesity, and support the hypothesis that genetics moderate the association between food reinforcement and BMI.
Asunto(s)
Índice de Masa Corporal , Alimentos , Monoaminooxidasa/genética , Polimorfismo de Nucleótido Simple/genética , Receptor de Serotonina 5-HT2A/genética , Refuerzo en Psicología , Adolescente , Adulto , Catecol O-Metiltransferasa/genética , Condicionamiento Operante/fisiología , Ingestión de Alimentos/genética , Ingestión de Energía/fisiología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Receptores Dopaminérgicos/genética , Estrés Psicológico/genética , Encuestas y Cuestionarios , Tirosina 3-Monooxigenasa/genética , Adulto JovenRESUMEN
Animal studies have shown dopamine transporter protein (DAT1) knock out mice are growth retarded and hyperactive. DAT1 has been researched in several human psychiatric studies with varying results regarding phenotype and DAT1 alleles. However, the relationship between DAT1 and short stature in humans has not been explored. Buccal swabs were collected from patients receiving growth hormone (GH) therapy and were genotyped for variable number tandem repeat (VNTR) by polymerase chain reaction. Forty subjects were included; twenty-three patients had the 10/10 DAT1 genotype and thirteen had the 9/10 genotype. Fifteen of the patients with the 10/10 genotype tested GH deficient. Seven patients with the 9/10 genotype tested GH sufficient. The linear growth rate during the first year of GH therapy was equivalent in both genotypes. In conclusion, polymorphisms in the DAT1 40 base pair (bp) VNTR genotype do not predict GH deficiency or response to GH therapy in short children.
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Genotipo , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Adolescente , Alelos , Estatura , Niño , Femenino , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/terapia , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Masculino , Valor Predictivo de las PruebasRESUMEN
The authors measured food reinforcement, polymorphisms of the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes, and laboratory energy intake in 29 obese and 45 nonobese humans 18-40 years old. Food reinforcement was greater in obese than in nonobese individuals, especially in obese individuals with the TaqI A1 allele. Energy intake was greater for individuals high in food reinforcement and greatest in those high in food reinforcement with the TaqI A1 allele. No effect of the DAT1 genotype was observed. These data show that individual differences in food reinforcement may be important for obesity and that the DRD2 genotype may interact with food reinforcement to influence energy intake.