Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

Introduction: Dopamine (DA) is a neurotransmitter that regulates the rewarding and motivational processes underlying food intake and eating behaviors. This study hy-pothesized associations of DNA methylation signatures at genes modulating DA sign -aling with obesity features, metabolic profiles, and...

Descripción completa

Detalles Bibliográficos
Autores: Ramos-López, O. (Omar)|||/items/40f32b89-391b-4e9a-aca7-948596cbfe94, Riezu-Boj, J.I. (José Ignacio)|||/items/87349e89-7360-4cdd-81be-2e8a6174b5f6, Milagro-Yoldi, F.I. (Fermín Ignacio)|||/items/07cf7af6-1f5f-4720-8c14-5197a7a724eb, Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/64945
Acceso en línea:https://hdl.handle.net/10171/64945
Access Level:acceso abierto
Palabra clave:Diet
Dopamine
Epigenetics
Obesity
SLC18A1
SLC6A3
Descripción
Sumario:Introduction: Dopamine (DA) is a neurotransmitter that regulates the rewarding and motivational processes underlying food intake and eating behaviors. This study hy-pothesized associations of DNA methylation signatures at genes modulating DA sign -aling with obesity features, metabolic profiles, and dietary intake.Methods: An adult population within the Methyl Epigenome Network Association project was included (n = 473). DNA methylation levels in white blood cells were measured by microarray (450K). Differentially methylated genes were mapped within the dopaminergic synapse pathway using the KEGG reference database (map04728). Subsequently, network enrichment analyses were run in the pathDIP portal. Associations of methylation patterns with anthropometric markers of general (BMI) and abdominal obesity (waist circumference), the blood metabolic profile, and daily dietary intakes were screened.Results: After applying a correction for multiple comparisons, 12 CpG sites were strongly associated (p <0.0001) with BMI: cg03489495 (ITPR3), cg22851378 (PPP2R2D), cg04021127 (PPP2R2D), cg22441882 (SLC18A1), cg03045635 (DRD5), cg23341970 (ITPR2), cg13051970 (DDC), cg08943004 (SLC6A3), cg20557710 (C ACNA1C), cg24085522 (GNAL), cg16846691 (ITPR2), and cg09691393 (SLC6A3). Moreover, average methylation levels of these genes differed according to the pres -ence or absence of abdominal obesity. Pathway analyses revealed a statistically sig-nificant contribution of the aforementioned genes to dopaminergic synapse transmission (p =4.78E−08). Furthermore,SLC18A1 and SLC6A3 gene methylation signatures correlated with total energy (p <0.001) and carbohydrate (p <0.001) intakes.Conclusions: The results of this investigation reveal that methylation status on DA signaling genes may underlie epigenetic mechanisms contributing to carbohydrate and calorie consumption and fat deposition.