Novel Epigenetic Changes Unveiled by Monozygotic Twins Discordant for Smoking Habits |
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Authors: | Alessandra Allione Francesca Marcon Giovanni Fiorito Simonetta Guarrera Ester Siniscalchi Andrea Zijno Riccardo Crebelli Giuseppe Matullo |
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Institution: | 1. Human Genetics Foundation, HuGeF, Turin, Italy.; 2. Department of Medical Sciences, University of Turin, Turin, Italy.; 3. Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.; UCLA-DOE Institute for Genomics and Proteomics, UNITED STATES, |
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Abstract: | Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population. |
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