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Donostia / San Sebastián, Spain

Gomez-Uriz A.M.,University of Navarra | Goyenechea E.,Instituto Biodonostia Donostia | Campion J.,University of Navarra | Campion J.,CIBER ISCIII | And 17 more authors.
Journal of Physiology and Biochemistry | Year: 2014

Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70±12 years old), and BMI (12 normal-weight/12 obese;mean 28.1±6.7 kg/m2). Blood cell DNAwas isolated and DNA methylation levels of TNF-α (-186 to +349 bp) and PON (-231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (-297 to -185). Total TNF-α promoter methylation was lower in stroke patients (p<0.001) and showed no interaction with body composition (p=0.807). TNF-á and PON total methylation levels correlated each other (r=0.44; p=0.031), especially in stroke patients (r=0.72; p=0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p=0.027) and the region containing three CpGs (from -170 to -162 bp) to the percentage of lipid intake and dietary indexes (p<0.05) in non-stroke patients. Themethylation of PON +15 and +241 CpGs was related to body weight (p=0.021), waist circumference (p=0.020), and energy intake (p=0.018), whereas +214 was associated to the quality of the diet (p<0.05) in nonstroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients. © University of Navarra 2014.

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