Tobacco smoking, a risk factor for several human diseases, can lead to alterations in DNA methylation. Smoking is a key source of cadmium exposure; however, there are limited studies examining DNA methylation alterations following smoking-related cadmium exposure. To identify such cadmium exposure-related DNA methylation, we performed genome-wide DNA methylation profiling using DNA samples from 50 smokers and 50 non-smokers. We found that a total of 136 CpG sites (including 70 unique genes) were significantly differentially methylated in smokers as compared to that in non-smokers. The CpG site cg05575921 in the AHRR gene was hypomethylated (Δ ß > − 0.2) in smokers, which was in accordance with previous studies. The rs951295 (within RNA gene LOC105370802) and cg00587941 sites were under-methylated by > 15% in smokers, whereas cg11314779 (within CELF6) and cg02126896 were over-methylated by ≥ 15%. We analyzed the association between blood cadmium concentration and DNA methylation level for 50 smokers and 50 non-smokers. DNA methylation rates of 307 CpG sites (including 207 unique genes) were significantly correlated to blood cadmium concentration (linear regression P value < 0.001). The four significant loci (cg05575921 and cg23576855 in AHRR, cg03636183 in F2RL3, and cg21566642) were under-methylated by > 10% in smokers compared to that in non-smokers. In conclusion, our study demonstrated that DNA methylation levels of rs951295, cg00587941, cg11314779, and cg02126896 sites may be new putative indicators of smoking status. Furthermore, we showed that these four loci may be differentially methylated by cadmium exposure due to smoking.

中文翻译：

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吸烟相关的 DNA 甲基化与血液中的镉浓度有不同的相关性。

吸烟是多种人类疾病的危险因素，可导致 DNA 甲基化的改变。吸烟是镉暴露的一个主要来源；然而，关于吸烟相关镉暴露后 DNA 甲基化改变的研究有限。为了识别这种与镉暴露相关的 DNA 甲基化，我们使用 50 名吸烟者和 50 名非吸烟者的 DNA 样本进行了全基因组 DNA 甲基化分析。我们发现，与非吸烟者相比，吸烟者总共有 136 个 CpG 位点（包括 70 个独特基因）甲基化存在显着差异。吸烟者中AHRR基因中的 CpG 位点 cg05575921低甲基化 (Δ ß > − 0.2)，这与之前的研究一致。吸烟者中 rs951295（RNA 基因 LOC105370802 内）和 cg00587941 位点甲基化不足 15% 以上，而 cg11314779（CELF6内）和 cg02126896 甲基化过度 ≥ 15%。我们分析了 50 名吸烟者和 50 名非吸烟者的血镉浓度与 DNA 甲基化水平之间的关联。307个CpG位点（包括207个独特基因）的DNA甲基化率与血镉浓度显着相关（线性回归P值<0.001）。与非吸烟者相比，吸烟者的四个显着位点（AHRR中的 cg05575921 和 cg23576855、 F2RL3中的 cg03636183和 cg21566642）甲基化不足超过 10%。总之，我们的研究表明，rs951295、cg00587941、cg11314779 和 cg02126896 位点的 DNA 甲基化水平可能是吸烟状况的新推定指标。此外，我们发现这四个位点可能因吸烟导致的镉暴露而发生差异甲基化。