Tobacco smoking leads to extensive genome-wide changes in DNA methylation.

Tobacco smoking leads to extensive genome-wide changes in DNA methylation.
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烟草吸烟会导致全基因组甲基化的广泛变化。

DOI:
10.1371/journal.pone.0063812
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Illig T
Illig T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zeilinger S;Kühnel B;Klopp N;Baurecht H;Kleinschmidt A;Gieger C;Weidinger S;Lattka E;Adamski J;Peters A;Strauch K;Waldenberger M;Illig T

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吸烟等环境因素可能对DNA甲基化模式产生长期影响,这可能导致基因表达的变化,并在更广泛的背景下导致各种疾病的发展或进展。我们进行了一项表观基因组关联研究(EWA),比较了基于人群的KORA F4小组的1793名参与者中当前吸烟者、既往吸烟者和从不吸烟者的情况,并在KORA F3小组的479名参与者中进行了复制,该研究是通过450 K BeadChip进行的。从全血中获得的基因组DNA。我们在22个常染色体中观察到位点特异性甲基化程度的广泛差异(p值范围为9.31E-08至2.54E-182)作为吸烟的函数,吸烟解释的方差百分比范围为1.31至41.02。根据戒烟时间和包年,发现前吸烟者的甲基化水平接近从未吸烟者的水平。此外,在AHRR内观察到cg 05575921的甲基化特异性蛋白结合模式,其具有与吸烟相关的DNA甲基化的最高水平的可检测变化(-24.40%甲基化; p = 2.54E-182),表明基因表达的调节作用。  我们的研究结果证实了吸烟对人类机体的广泛影响,但也表明戒烟可能会恢复从不吸烟者的DNA甲基化状态。
Environmental factors such as tobacco smoking may have long-lasting effects on DNA methylation patterns, which might lead to changes in gene expression and in a broader context to the development or progression of various diseases. We conducted an epigenome-wide association study (EWAs) comparing current, former and never smokers from 1793 participants of the population-based KORA F4 panel, with replication in 479 participants from the KORA F3 panel, carried out by the 450K BeadChip with genomic DNA obtained from whole blood. We observed wide-spread differences in the degree of site-specific methylation (with p-values ranging from 9.31E-08 to 2.54E-182) as a function of tobacco smoking in each of the 22 autosomes, with the percent of variance explained by smoking ranging from 1.31 to 41.02. Depending on cessation time and pack-years, methylation levels in former smokers were found to be close to the ones seen in never smokers. In addition, methylation-specific protein binding patterns were observed for cg05575921 within AHRR, which had the highest level of detectable changes in DNA methylation associated with tobacco smoking (–24.40% methylation; p = 2.54E-182), suggesting a regulatory role for gene expression. The results of our study confirm the broad effect of tobacco smoking on the human organism, but also show that quitting tobacco smoking presumably allows regaining the DNA methylation state of never smokers.
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