DNA methylation of miRNA coding sequences putatively associated with childhood obesity

Autores: Mansego Talavera, María Luisa; García Lacarte, Marcos; Milagro Yoldi, Fermín Ignacio; Martí del Moral, Amelia; Martínez Hernández, Alfredo; GENOI members
Título de la revista: PEDIATRIC OBESITY
ISSN: 2047-6310
Volumen: 12
Número: 1
Páginas: 19 - 27
Fecha de publicación: 2017
Background: Epigenetic mechanisms may be involved in obesity onset and its consequences. The aim of the present study was to evaluate whether DNA methylation status in microRNA (miRNA) coding regions is associated with childhood obesity. Material and Methods: DNA isolated from white blood cells of 24 children (identification sample: 12 obese and 12 non-obese) from the Grupo Navarro de Obesidad Infantil study was hybridized in a 450K methylation microarray. Several CpGs whose DNA methylation levels were statistically different between obese and non-obese were validated by MassArray (R) in 95 children (validation sample) from the same study. Results: Microarray analysis identified 16 differentially methylated CpGs between both groups (6 hypermethylated and 10 hypomethylated). DNA methylation levels in miR-1203, miR-412 and miR-216A coding regions significantly correlated with body mass index standard deviation score (BMI-SDS) and explained up to 40% of the variation of BMI-SDS. The network analysis identified 19 well-defined obesity-relevant biological pathways from the KEGG database. MassArray (R) validation identified three regions located in or near miR-1203, miR-412 and miR-216A coding regions differentially methylated between obese and non-obese children. Conclusions: The current work identified three CpG sites located in coding regions of three miRNAs (miR-1203, miR-412 and miR-216A) that were differentially methylated between obese and non-obese children, suggesting a role of miRNA epigenetic regulation in childhood obesity.