Journal
HUMAN MOLECULAR GENETICS
Volume 23, Issue 9, Pages 2290-2297Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt621
Keywords
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Funding
- Swedish Medical Research Council [2011-2354]
- Swedish Society for Medical Research (SSMF)
- Goran Gustafssons Stiftelse
- Uppsala University
- Uppsala University Hospital
- Science for Life Laboratory (SciLife-Lab)-Uppsala
- Swedish Research Council [80576801, 70374401]
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Exposure to environmental and lifestyle factors, such as cigarette smoking, affect the epigenome and might mediate risk for diseases and cancers. We have performed a genome-wide DNA methylation study to determine the effect of smoke and snuff (smokeless tobacco) on DNA methylation. A total of 95 sites were differentially methylated [false discovery rate (FDR) q-values 0.05] in smokers and a subset of the differentially methylated loci were also differentially expressed in smokers. We found no sites, neither any biological functions nor molecular processes enriched for smoke-less tobacco-related differential DNA methylation. This suggests that methylation changes are not caused by the basic components of the tobacco but from its burnt products. Instead, we see a clear enrichment (FDR q-value 0.05) for genes, including CPOX, CDKN1A and PTK2, involved in response to arsenic-containing substance, which agrees with smoke containing small amounts of arsenic. A large number of biological functions and molecular processes with links to disease conditions are also enriched (FDR q-value 0.05) for smoke-related DNA methylation changes. These include insulin receptor binding, and negative regulation of glucose import which are associated with diabetes, positive regulation of interleukin-6-mediated signaling pathway, regulation of T-helper 2 cell differentiation, positive regulation of interleukin-13 production which are associated with the immune system and sertoli cell fate commitment which is important for male fertility. Since type 2 diabetes, repressed immune system and infertility have previously been associated with smoking, our results suggest that this might be mediated by DNA methylation changes.
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