Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells

Autores: Gómez Úriz, Ana; Milagro Yoldi, Fermín Ignacio; Mansego Talavera, María Luisa; Cordero Sánchez, Paul; Abete Goñi, Itziar; De-Arce, A.; Goyenechea Soto, Estíbaliz; Blázquez, V.; Martínez-Zabaleta, M.; Martínez Hernández, Alfredo; López-de-Munain, A.; Campión Zabalza, Francisco Javier
Título de la revista: HUMAN MOLECULAR GENETICS
ISSN: 0964-6906
Volumen: 24
Número: 5
Páginas: 1432 - 1440
Fecha de publicación: 2015
Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers.