Smoke-related DNA methylation changes in the etiology of human disease
Smoke-related DNA methylation changes in the etiology of human disease
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DOI：
10.1093/hmg/ddt621
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发表时间：
2014-05-01
影响因子：
3.5
通讯作者：
Johansson, Asa
中科院分区：
文献类型：
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作者：
Besingi, Welisane;Johansson, Asa
暴露于环境和生活方式因素，如吸烟，会影响表观基因组，并可能介导疾病和癌症的风险。我们进行了一项全基因组DNA甲基化研究，以确定烟和鼻烟（无烟烟草）对DNA甲基化的影响。吸烟者中共有95个位点存在差异甲基化[错误发现率（FDR） q值0.05]，其中一部分差异甲基化位点在吸烟者中也存在差异表达。我们没有发现与无烟烟草相关的差异DNA甲基化相关的位点，也没有发现任何生物功能或分子过程。这表明甲基化变化不是由烟草的基本成分引起的，而是由其燃烧产物引起的。相反，我们看到CPOX、CDKN1A和PTK2等基因明显富集（FDR q值0.05），涉及对含砷物质的反应，这与含有少量砷的烟雾一致。与吸烟相关的DNA甲基化变化也丰富了大量与疾病状况相关的生物学功能和分子过程（FDR q值0.05）。这些包括胰岛素受体结合，葡萄糖输入的负调节这与糖尿病有关，白细胞介素6介导的信号通路的正调节，t -辅助2细胞分化的调节，白细胞介素13产生的正调节这与免疫系统和支持细胞命运承诺有关这对男性生育能力很重要。由于2型糖尿病、免疫系统抑制和不孕症先前与吸烟有关，我们的研究结果表明，这可能是由DNA甲基化变化介导的。
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.