Silvia Stringhini1, Silvia Polidoro2, Carlotta Sacerdote2, Rachel S Kelly3, Karin van Veldhoven4, Claudia Agnoli5, Sara Grioni5, Rosario Tumino6, Maria Concetta Giurdanella6, Salvatore Panico7, Amalia Mattiello7, Domenico Palli8, Giovanna Masala8, Valentina Gallo9, Raphaële Castagné10, Fred Paccaud11, Gianluca Campanella12, Marc Chadeau-Hyam10, Paolo Vineis4. 1. Institute of Social and Preventive Medicine, University Hospital Centre, Lausanne, Switzerland, silvia.stringhini@chuv.ch. 2. Human Genetics Foundation (HuGeF), Torino, Italy. 3. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. 4. Human Genetics Foundation (HuGeF), Torino, Italy, MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK. 5. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 6. Cancer Registry, ASP Ragusa, Italy. 7. Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. 8. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. 9. Centre of Primary Care and Public Health Blizard Institute Queen Mary, University of London, UK and Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom. 10. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK. 11. Institute of Social and Preventive Medicine, University Hospital Centre, Lausanne, Switzerland. 12. Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Abstract
BACKGROUND: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. METHODS: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. RESULTS: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. CONCLUSIONS: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk.
BACKGROUND: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. METHODS: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. RESULTS: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. CONCLUSIONS: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk.
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