Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells
Keywords: 
Obesity
Ischemic stroke
White blood cells
KCNQ1
Materias Investigacion::Ciencias de la Salud::Nutrición y dietética
Materias Investigacion::Ciencias de la Salud::Cardiología
Issue Date: 
2015
Publisher: 
Oxford University Press
Project: 
Ministerio de Ciencia e Innovación of Spain (project referenced SAF2010-16887)
Línea Especial about Nutrition, Obesity and Health (University of Navarra LE/97)
CIBERobn and CIBERNED (Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Madrid, Spain)
ISSN: 
0964-6906
Editorial note: 
This is a pre-copyedited, author-produced PDF of an article accepted for publication in 'Human Molecular Genetics' following peer review. The version of record: "Gómez-Úriz AM, Milagro FI, Mansego-Talavera ML, Cordero P, Abete I, De-Arce A, et al. Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells. Hum Mol Genet 2015;24(5):1432-1440", is available online at http://dx.doi.org/10.1093/hmg/ddu559
Citation: 
Gómez-Úriz AM, Milagro FI, Mansego-Talavera ML, Cordero P, Abete I, De-Arce A, et al. Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells. Hum Mol Genet 2015;24(5):1432-1440
Abstract
ABSTRACT 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 BMI. 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 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 PM20D1 gene was significantly hypermethylated in stroke patients. One CpG site at CALD1 gene showed an interaction between stroke and obesity. Two CpGs located in the genes WT1 and 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.

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