Dopamine Regulating Genes, Negative Stressors, and Energy Balance Behaviors Among Chinese Adolescents

Context: Dopamine has been implicated as an important neurotransmitter involved in regulating appetite and food intake by modulating the reinforcement of food via the meso-limbic circuitry of the brain. Several genes have been linked with the regulation of dopamine. Monoamine oxidase A (MAOA) modulates the metabolism of serotonin and dopamine, both of which are neurotransmitters involved in the regulation of appetite and food intake. The gene coding for MAOA contains a 30-bp tandem repeat (uVNTR) polymorphism in its promoter region that has been previously identified to be associated with energy balance behaviors and body mass index (BMI). The gene coding for dopamine receptor D4 (DRD4) contains a 16 amino acid (48-bp) repeat polymorphism that has been linked with food consumption and BMI. Lastly, the dopamine transporter gene (SLC6A3: Solute carrier family 6 – neurotransmitter transporter, dopamine – member 3) codes for a dopamine transporter protein (DAT) that mediates the active reuptake of dopamine from the synapse. The transport gene contains a 40-base variable number tandem repeat (VNTR) at the 3’ untranslated region (3’-UTR) that has been previously identified to be associated with variable levels of postsynaptic dopamines. Objective: Our goals were to investigate the population effects of the aforementioned functional polymorphisms on various types of food consumption (soda, fast food, snack, and ready to eat foods) and physical activity (exercise and TV watching), and to further explore gender differences and interaction effects with negative stressors. Methods: The analyses were conducted with data on genotypes and self-reported behavioral characteristics among 951 Chinese adolescents 11-15 years old living in Wuhan, China. Results: Males with the high-activity allele of MAOA had lower odds of increased soda intake (adjusted OR=0.63; 95% CI: 0.41-0.98, p=0.03) than those with low activity allele. Experience of negative stressors significantly strengthened the protective genetic effect on increasing odds of engaging in vigorous activity (adjusted OR for interaction=1.89 with 95% CI of 1.89-2.52, pvalue for interaction=0.04). Additionally, combined males and females with DRD4 variant had greater odds of engaging in vigorous exercise (adjusted OR=1.39; 95% CI: 1.01-1.86, p=0.03) and of increased soda intake (adjusted OR=1.33; 95% CI: 1.01-1.76, p=0.04) than those with the wild-type allele. Among females, wild-type carriers (no 2R or 7R allele) when exposed to negative stressors were significantly more likely to engage in vigorous exercise (adjusted OR=0.14, 95% CI: 0.047-0.43, p=0.000586). Lastly, combined males and females with the DAT variant had increased odds of watching TV (adjusted OR=1.59; 95% CI: 0.61-1.77) and decreased odds of consuming fast foods (adjusted OR=0.60; 95% CI: 0.38-0.95, p=0.030654) than those with DAT wild-type. Experience of negative stressors significantly weakened the protective genetic effect on the odds for fast food consumption (adjusted OR=0.30; 95% CI: 0.13-0.66, p=0.002639). Conclusions: Our findings confirm the genetic effects of the dopamine regulating genes polymorphisms on food consumption and physical activity, and provide new insights about interactions with negative stressors