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Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake

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Abstract

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 DNA was 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-α 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. The methylation 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 non-stroke 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.

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Acknowledgments

Authors wish to thank to all patients who volunteered to participate in this study.

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Authors and Affiliations

  1. Department of Nutrition, Food Sciences and Physiology, University of Navarra, Pamplona, Spain

    A. M. Gómez-Uriz, J. Campión, B. Puchau, F. I. Milagro & J. A. Martínez

  2. CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain

    J. Campión, F. I. Milagro & J. A. Martínez

  3. Neuroscience Area, Instituto Biodonostia Donostia, Donostia-San Sebastian, Spain

    E. Goyenechea, A. de Arce, M. T. Martinez, I. Abete & A. Lopez de Munain

  4. Department of Neurology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain

    A. de Arce, M. T. Martinez & A. Lopez de Munain

  5. Department of Neurology, Neurovascular Unit, Hospital Universitario Donostia, Donostia-San Sebastian, Spain

    A. de Arce, M. T. Martinez & A. Lopez de Munain

  6. CIBERNED Ministry of Economy and Competitiveness, Institute Carlos III, Barcelona, Spain

    A. de Arce, M. T. Martinez & A. Lopez de Munain

  7. Department of Neurosciences, University of the Basque Country UPV/EHU, San Sebastián, Spain

    M. T. Martinez & A. Lopez de Munain

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  1. A. M. Gómez-Uriz
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  2. E. Goyenechea
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  3. J. Campión
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  4. A. de Arce
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  8. I. Abete
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  9. J. A. Martínez
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  10. A. Lopez de Munain
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Correspondence to J. Campión.

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A.M. Gómez-Uriz and E. Goyenechea contributed equally to this work.

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Gómez-Uriz, A.M., Goyenechea, E., Campión, J. et al. Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake. J Physiol Biochem 70, 603–614 (2014). https://doi.org/10.1007/s13105-014-0316-5

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  • DOI: https://doi.org/10.1007/s13105-014-0316-5

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